bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated limb perfusion for melanoma: Effectiveness and toxicity of cisplatin compared with that of melphalan and other drugs
Authors: Thompson John F. , Gianoutsos Mark P. 
Published: August 2005

AbstractIn patients with advanced or recurrent melanoma confined to a limb, hyperthermic isolated limb perfusion (ILP) with melphalan produces complete remission in 35–40% of cases and partial remission in a further 35–40%. Mild or moderate limb toxicity is usual, but severe toxic reactions in the limb sometimes occur. After preliminary reports suggested that cisplatin administered by ILP was even more effective than melphalan yet less toxic, a study was undertaken to further assess the value of hyperthermic ILP with cisplatin in the management of limb melanoma. Ten patients were treated. The procedure failed to eliminate melanoma in the limb in 5 of the 6 who received therapeutic ILPs for recurrent disease, and recurrence developed in 2 of the 4 patients who received prophylactic ILPs. Toxicity in the perfused limbs was unacceptably high, with 2 of the 10 patients having severe reactions, one necessitating amputation. We conclude from the results of this study and from a review of literature that neither cisplatin nor any other drug or drug combination so far used for ILP in melanoma patients achieves results which are clearly superior to those achieved with melphalan. Studies are currently in progress investigating double perfusion protocols, new strategies with regional hyperthermia, and the administration by ILP of biological response modifiers such as tumor necrosis factor and interferon. However, for the present, hyperthermic ILP with melphalan remains the treatment most likely to be successful in eliminating or controlling advanced or recurrent melanoma in a limb.
Controversies concerning adjuvant regional isolated perfusion for stage I melanoma of the extremities
Authors: Koops Heimen Schraffordt , Kroon Bin B. R. , Oldhoff Jan , Hoekstra Harald J. 
Published: August 2005

AbstractThe use of isolated perfusion with melphalan in an adjuvant setting for stage I extremity melanoma continues to be controversial. In this article, 2 retrospective studies compare patients undergoing perfusion from Groningen, the Netherlands, with matched controls from the Sydney Melanoma Unit in Australia and from 5 hospitals in the Netherlands and Westphalia (a region of Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or more in thickness. In the first study, women with a melanoma of the leg (excluding the foot) and treated with perfusion had a significantly higher survival than women treated with local excision alone. In the second study, a proportional hazards regression analysis for recurrent disease and survival identified no statistically significant difference in favor of adjuvant perfusion.Two other studies from the literature evaluating the efficacy of perfusion are examined. Patients treated at the M.D. Anderson Cancer Center, Houston, with wide local excision and perfusion are compared retrospectively with a group of patients individually matched for prognostic factors from the University of Alabama in Birmingham, U.S.A. and the Sydney Melanoma Unit. A small subset of patients with tumors >2 mm thick benefited from perfusion. A prospective randomized study from the University Hospital, Cologne, West Germany found benefits for all perfused patients with tumors >1.5 mm but their patients did not appear to be individually matched for tumor thickness.It is concluded after critical appraisal of all these studies that there is insufficient convincing evidence to date of an advantage of perfusion over wide local excision alone.
Hereditary melanoma and the search for the melanoma gene
Authors: Kefford Richard F. 
Published: August 2005

AbstractThe discovery and characterization of growth regulatory genes, in the form of oncogenes, and their counterparts, tumor suppressor (TS) or antioncogenes, has vastly expanded the basic understanding of tumorigenesis. Human solid tumors, such as colorectal cancer, for which the molecular genetics have been most clearly defined, display progressive evolution from cellular dysplasia to anaplasia and metastasis through the stepwise accumulation of genetic defects, involving the regulation and expression of both oncogenes and TS genes. The study of basic genetic abnormalities in melanoma and the identification of the most fundamental of these is critical both to the understanding of abnormal melanocyte proliferation and its potential pharmacologic or immunologic regulation, and also to the identification and screening of patients at high risk for the development of melanoma. The search for such genetic abnormalities has included an analysis of melanomas for defects in known characterized oncogenes and TS genes, and, more importantly, the use of families with hereditary melanoma (HM) and dysplastic nevi in an endeavor to find the melanoma gene. The importance of HM is fundamental, since in the case of other hereditary cancer syndromes for which the genetic basis has been identified, the same or similar genetic abnormalities underlie sporadic tumors of the same tissue type. Thus HM is likely to be the major signpost to the melanomagenic defect.
Active immunotherapy with viral lysates of micrometastases following surgical removal of high risk melanoma
Authors: Hersey Peter 
Published: August 2005

AbstractPatients who develop lymph node metastases from melanoma are known to be at risk of developing further recurrences from melanoma following surgical removal of lymph node metastases. The purpose of the present study was to examine whether immunization over a 2 year period with a vaccine made from vaccinia viral lysates of an allogeneic melanoma cell (VMCL), following surgical removal of lymph node metastases, would help prevent the development of distant metastases and improve survival from the disease. Eighty patients treated with VMCL alone and followed for a minimum of 5.5 years had improved survival compared to a historical control group of 151 patients and a concurrent non‐randomized group of 55 patients. Similarly, the survival of 102 patients treated with VMCL + low dose cyclophosphamide for a minimum of 3.5 years was superior to that of the historical control group but not to that of the VMCL alone treated group. Improvement in survival was still evident when this was measured from the date of removal of the primary tumor. Analysis of subsets of patients showed that VMCL treatment appeared to benefit patients irrespective of the number of lymph nodes involved and whether surgery was carried out near to (synchronous metastases) or some time after removal of the primary delayed metastases). Analysis of the effect of treatment on duration to development of distant metastases suggested that there was a lower proportion of metastases during treatment with VMCL compared to the historical control groups. Treatment with VMCL also appeared to be associated with a lower incidence of cutaneous metastases but a higher proportion of visceral (including liver) metastases. Treatment was not associated with prolongation of survival after development of distant metastases. The results from this prolonged follow‐up provide further support for an apparent survival benefit from immunotherapy with VMCL and suggest that the duration to and site of distant metastases is altered by this treatment. A randomized control (Phase III) study based on these results is in progress.
Immunotherapy with monoclonal antibodies in metastatic melanoma
Authors: Steffens Thomas A. , Bajorin Dean F. , Houghton Alan N. 
Published: August 2005

AbstractTherapy for metastatic melanoma has been disappointing to date. Treatment with chemotherapy only uncommonly results in complete responses and rarely results in long‐term survivors. The identification of human melanoma cell surface antigens has led to the development of an array of mouse monoclonal antibodies (MAb) for use in the diagnosis and therapy of patients with metastatic melanoma. Strategies utilizing MAbs based on immunologic approaches have been developed. Naked MAbs directed against glycoprotein surface antigens or conjugated to toxins or radionuclides have shown little biologic or clinical activity. However, phase I studies of MAb directed against glycolipid antigens have yielded objective tumor shrinkage with occasional complete responses. Severe toxicity has been seen infrequently. Possible anti‐tumor mechanisms include complement activation and antibody‐dependent cellular cytotoxicity utilizing natural killer cells or monocytes as effector cells. Strategies to enhance the anti‐tumor effects of MAb, including combinations with cytotoxic agents and cytokines, have been introduced with limited success thus far. The development of a human IgG anti‐mouse antibody has been seen in nearly all treated patients. A new generation of MAb engineered to overcome the immunogenicity of mouse MAb and to enhance immune effector function will soon enter clinical trials.
Therapy of disseminated melanoma by liposome‐activated macrophages
Authors: Fidler Isaiah J. 
Published: August 2005

AbstractThe uncontrolled growth of metastases is a major cause of death from melanoma. Metastases arise from the nonrandom spread of specialized malignant cells that preexist within a primary neoplasm. Macrophages are activated to become tumoricidal by interaction with phospholipid vesicles (liposomes) containing immunomodulators recognize and destroy neoplastic cellsin vitro andin vivo while leaving nonneoplastic cells unharmed. The mechanism(s) by which macrophages discriminate between tumorigenic and normal cells is independent of tumor cell characteristics such as immunogenicity, metastatic potential, and sensitivity to cytotoxic drugs. Moreover, macrophage destruction of tumor cells apparently is not associated with the development of tumor cell resistance.Intravenously administered liposomes are cleared from the circulation by phagocytic cells. The administration of such liposomes has been shown to activate macrophagesin situ and to bring about eradication of cancer metastases in several experimental tumor systems and in dogs with spontaneous osteogenic sarcoma. Macrophage destruction of metastasesin vivo is significant, provided that the tumor burden at the start of treatment is minimal. For this reason, we have been investigating various methods to achieve maximal cytoreduction in metastases by modalities such as chemotherapy or radiotherapy prior to systemic activation of macrophages. Macrophage‐directed therapy has been studied in several human protocols, yielding important biological information about the safe use of liposome‐encapsulated macrophage activators in cancer patients.
Systemic chemotherapy for malignant melanoma
Authors: Coates Alan S. 
Published: August 2005

AbstractMalignant melanoma is notoriously resistant to chemotherapy. Standard single agents include dacarbazine and the nitrosoureas, but most series treating patients with metastatic melanoma report response rates of about 20%. Occasional patients, however, achieve long term remission, amounting to cure, after such treatment. Adjuvant studies have failed to define any systemic therapy of value after surgery for primary or regional lymph node disease. Combinations of drugs have not been shown to be superior to single agents. Cisplatin and fotemustine are among the newer agents with activity. Isolated limb perfusion with melphalan and systemic therapy with high dose alkylating agents and marrow transplantation suggest that the resistance to conventional concentrations of alkylating agents is not absolute. One strategy to improve the efficacy of alkylating agents may therefore be the modulation of cellular glutathione or glutathione‐S‐transferase. Biological response modifiers remain of interest, though many of the protocols with the best response rates are impractical for routine use. Many patients with asymptomatic metastatic melanoma should be observed without treatment. Outside clinical trials, it is reasonable to use single agent dacarbazine or lomustine if chemotherapy is required.
Epidemiology of gastro‐esophageal reflux disease
Authors: Howard P. J. , Heading R. C. 
Published: August 2005

AbstractGastro‐esophageal reflux disease encompasses a spectrum of disorders in which gastric reflux leads to symptoms and/or damage to the esophageal mucosa. Although a common problem in clinical practice, our understanding of the pathophysiology of the condition has not been matched by our knowledge of its epidemiology and natural history. This review examines some of the difficulties inherent in epidemiological studies with particular emphasis on the nature and variety of reflux symptoms and their relationship to esophagitis, the natural history and complications of reflux disease, Barrett's esophagus, and the possible role of gastroesophageal reflux in lung disease, especially asthma.
Maintenance therapy: Is there still a place for antireflux surgery?
Authors: Armstrong David , Nicolet Marcel , Monnier Phillippe , Chapuis Germain , Savary Marcel , Blum André L. 
Published: August 2005

AbstractEffective and safe maintenance medical therapy for uncomplicated reflux esophagitis is now feasible with omeprazole and it is likely that other H+K+ ATPase blockers, and possibly very high dose H2 receptor antagonist regimens, will also be acceptable. In addition, many patients with ulceration, strictures, and Barrett's esophagus will respond to conservative medical therapy and a proportion of patients with erosive esophagitis may remain in remission with cisapride or with low dose H2 receptor antagonists, if disease is less severe. Thus, there is now a medical “gold standard” against which surgical therapy for uncomplicated esophagitis must be judged and it is essential that all future studies be conducted with clearly defined criteria for the assessment of the symptoms and endoscopic signs of esophagitis and its complications.As ever, the patient's wishes are paramount, but he or she must be allowed to select his or her therapy on the basis of a balanced and fully informed assessment of the long‐term and short‐term risks of all therapeutic modalities. The burdensome prospect of lifelong tablet ingestion and its potential dangers must be weighed against the alternative, in up to 30% of cases, that surgery may produce dysphagia, gas bloat, or dumping with no guarantee of a long‐term cure.
Does modern technology belong in gastro‐intestinal surgery? A step from subjective perception to objective information
Authors: Hill Lucius D. , Kraemer Stefan J. M. 
Published: August 2005

AbstractThe intra‐operative measurement of lower esophageal sphincter (LES) pressure can aid the surgeon in primary repair of the gastroesophageal junction. We evaluated 1,000 patients undergoing primary repairs; 540 patients underwent surgery before the introduction of LES pressure measurements and 460 patients after LES pressure measurement. The incidence of continued reflux was lower in the group having intraoperative LES pressure measurement (4.5% vs. 1.5%). The incidence of continued reflux in this group has been <1%. The measurement of intra‐operative LES pressure brings objective technology to our patients and improves their quality of life.
Endoscopic control of gastro‐esophageal reflux: Status report
Authors: Donahue Philip E. , Sugitani Atsushi , Carvalho Paulo 
Published: August 2005

AbstractGastro‐esophageal reflux disease is a common disorder which sometimes requires surgical treatment. Until recently, surgical treatment was the only alternative for severe complications of reflux. During the past 5 years endoscopic treatments for reflux have been reported from several medical centers. These new approaches may herald a new era for the treatment of reflux complications. However, at this time they are purely experimental approaches.Since physiologic antireflux mechanisms involve the muscles of the proximal gastric cardia as well as those of the lower esophageal sphincter, it is not surprising that endoscopic treatments have been directed at these two areas. However, the first endoscopic attempts at reflux control were directed at the lower esophagus sphincter. The most recent efforts at endoscopic control have been aimed at the proximal stomach, based on the concept that scarification beneath the lower end of the esophagus reduces the amount or frequency of reflux. Neither of these latter approaches has been reported in human patients.Since all endoscopic approaches are potentially dangerous, we recommend the adoption of a rigorous protocol for all human application. A possible protocol for this purpose is described herein; the authors will provide data analysis for any cohort of patients receiving endoscopic therapy, and will provide the results of all endoscopic treatments to any serious investigators.
What is the place of antrectomy with Roux‐en‐Y in the treatment of reflux disease? Experience with 83 total duodenal diversions
Authors: Fekete F. , Pateron D. 
Published: August 2005

AbstractAntrectomy with Roux‐en‐Y gastrojejunostomy was performed in 83 patients with “complicated” forms of peptic esophagitis. The esophagitis was considered complicated either because of the severity of the lesions (stricture, brachyesophagus, or endobrachyesophagus) or because of postoperative conditions after one or more previous operations (Heller's myotomy, esophagogastric resections, or hiatal hernia repair).A standard procedure was performed in 56 patients while technical adjustments were required for 27 patients who had previously undergone surgery. Two patients died from pulmonary embolism. Early postoperative complications occurred in 11% of patients. Healing of esophagitis was observed for all the patients treated with the standard procedures. Six partial regressions and 1 complete regression of Barrett's mucosa were observed. Digestive sequellae were minor and decreased with time. Assessment of pH and small bowel manometry showed that the reflux was controlled and no small bowel motility disturbance was observed when the standard technique was used including a small gastric resection. The main digestive sequellae, including lack of healing of esophagitis, dumping syndrome, and gastrojejunal anastomotic ulcer, occurred when a two‐thirds gastrectomy was performed in order to avoid vagotomy.
The quality of life following antireflux surgery
Authors: Pope Charles E. 
Published: August 2005

AbstractTo improve the quality of life after antireflux surgery, the patient should notice improvement or disappearance of the symptoms leading to the surgery and should not acquire any new symptoms resulting from antireflux surgery. Published accounts of antireflux surgery results vary widely. Part of this variation may be due to nonstandard methods of evaluating symptoms. A system of symptom evaluation is proposed which takes into account the intensity and frequency of symptoms. It is hoped that this system will allow surgeons to refine and improve their techniques and results.
Surgical management after failed antireflux operations
Authors: Skinner David B. 
Published: August 2005

AbstractFrom 1973 to 1989, 117 (28%) patients underwent re‐operation for failed antireflux surgery from a total of 413 esophagogastric operations for gastro‐esophageal reflux disease. Seventy‐eight patients who underwent re‐operation before 1984 were reviewed in detail for classification and long‐term outcome. Forty re‐operations followed a failed Nissen fundoplication, while no other procedure was the most recent prior operation in more than 10 patients. Re‐operation rates were 3% following prior surgery in our clinic for reflux disease other than stricture and 9.6% if the prior operation was done for stricture. There was no difference in re‐operation rates for the Belsey Mark IV or Nissen fundoplication, the 2 most commonly used repairs. In each case, complete pre‐operative evaluations included symptom score, radiography, endoscopy, and esophageal function tests. Based on the results, the 78 patients were classified as pure sphincter mechanism failure to stop reflux (n=14), pure esophageal clearance failure (n=12), combined sphincter mechanism failure and clearance failure (n=29), alkaline reflux (n=9), or no reflux but another condition found (n=14). Patients having symptoms following a prior Nissen fundoplication or Angelchik prosthesis insertion were more likely to have esophageal clearance failure than those having other repairs. The classification proved to be a useful guide to the need for and types of re‐operation chosen. Among the 117 patients undergoing re‐operation, there were 2 (1.7%) deaths within 3 months of surgery and 25 (21%) complications. Long‐term results were directly related to the number of previous operations, with resection and intestinal interposition being the preferred procedure in patients having had 2 or more previous attempts at antireflux surgery.
Quantifying Bioactivity on a Large Scale: Quality Assurance and Analysis of Multiparametric Ultra-HTS Data
Authors: Heyse Stephan , Brodte Annette , Bruttger Oliver , Duerr Oliver , Freeman Tobe , Jung Tom , Lindemann Michael , Ottl Johannes , Rinn Bernd 
Published: August 2005

There is a growing need to precisely quantify the selectivity of large compound sets in high throughput screening, directing investment in lead optimization towards compounds with a high chance of success. High-content, high-density screening technologies such as multiparametric ultra-HTS provide a basis for highly precise screening with unprecedented scope for delineating process artifacts from reliable signals. However, the full potential of these technologies can only be realized with suitable experimental design and sophisticated data analysis tools. We present two advanced analysis workflows demonstrating how multiparametric readouts from a high throughput primary screen can improve decision quality in the hit identification process. The first involves discrete thresholding and the application of multiple selection criteria. The second uses machine learning algorithms and allows an unbiased consideration of all measured parameters.
Rab11 GTPase-Regulated Membrane Trafficking Is Crucial for Tip-Focused Pollen Tube Growth in Tobacco
Authors: de Graaf Barend H.J. , Cheung Alice Y. , Andreyeva Tatyana , Levasseur Kathryn , Kieliszewski Marcia , Wu Hen-ming 
Published: August 2005

AbstractPollen tube growth is a polarized growth process whereby the tip-growing tubes elongate within the female reproductive tissues to deliver sperm cells to the ovules for fertilization. Efficient and regulated membrane trafficking activity incorporates membrane and deposits cell wall molecules at the tube apex and is believed to underlie rapid and focused growth at the pollen tube tip. Rab GTPases, key regulators of membrane trafficking, are candidates for important roles in regulating pollen tube growth. We show that a green fluorescent protein–tagged Nicotiana tabacum pollen-expressed Rab11b is localized predominantly to an inverted cone-shaped region in the pollen tube tip that is almost exclusively occupied by transport vesicles. Altering Rab11 activity by expressing either a constitutive active or a dominant negative variant of Rab11b in pollen resulted in reduced tube growth rate, meandering pollen tubes, and reduced male fertility. These mutant GTPases also inhibited targeting of exocytic and recycled vesicles to the pollen tube inverted cone region and compromised the delivery of secretory and cell wall proteins to the extracellular matrix. Properly regulated Rab11 GTPase activity is therefore essential for tip-focused membrane trafficking and growth at the pollen tube apex and is pivotal to reproductive success.