bluuebunny/crossref_metadata_2025 huggingface dataset:
Embolization of Renal Artery Aneurysm and Arteriovenous Fistula
Authors: Trocciola Susan M. , Chaer Rabih A. , Lin Stephanie C. , Dayal Rajeev , Scherer Matthew , Garner Matthew , Coll Deidre , Kent K. Craig , Faries Peter L.
Published: March 2006

A renal artery aneurysm with an associated arteriovenous fistula in a native kidney has been reported infrequently in the literature. Management depends on size, location, and the patient's physiological condition. We describe a case in which endovascular therapy was used to successfully exclude both aneurysm and fistula. This report describes a 13-centimeter renal artery aneurysm with arteriovenous fistula originating from an isolated branch of the renal artery. Coil-embolization resulted in thrombosis of the aneurysm and fistula while preserving parenchymal perfusion. Coil embolization is an alternative to surgery for coexistent renal artery aneurysm and arteriovenous fistula arising from a branch of adequate length for placement of embolic coils. Successful treatment is not limited by aneurysm size or presence of arteriovenous connection.
Aortic Graft Infection: Update on Management and Treatment Options
Authors: Perera Ganesha B. , Fujitani Roy M. , Kubaska Stephen M.
Published: March 2006

Replacement of the abdominal aorta, whether by autogenous or prosthetic conduit, has been an a priori requisite in the vascular surgeon's armamentarium since its technical feasibility was described in the early 1950s. The Achilles' heel of this operation, in spite of the progress made over the last half century, is still, however, aortic graft infection. Though survival and limb salvage rates have improved over time—commensurate with advances in surgical technique, critical care, and antimicrobial agents—the prevention and treatment of aortic graft infection remains a formidable challenge to the vascular surgeon. The authors herein review the current literature on this topic with an emphasis on the surgical management options available and suggest an individualized operative strategy based on patient as well as microbial factors to attain the best possible outcome.
Endovascular Therapy of Symptomatic Innominate-Subclavian Arterial Occlusive Lesions
Authors: Woo Edward Y. , Fairman Ronald M. , Velazquez Omaida C. , Golden Michael A. , Karmacharya Jagajan , Carpenter Jeffrey P.
Published: March 2006

The purpose of this study was to determine the safety and efficacy of angioplasty and stenting for symptomatic innominate-subclavian lesions by review of records of symptomatic patients undergoing angioplasty and stenting of high-grade lesions (>80%) of the innominate and subclavian arteries. Follow-up consisted of history (symptoms) and physical examination (pulses and blood pressures) at 1, 3, 6, and then every 12 months plus an annual duplex ultrasound examination. Between 1998 to 2003, 25 patients (27 lesions) were treated. Ages ranged from 48 to 89 years. Symptoms included vertebrobasilar/steal (15), claudication (6), ischemia (4), and coronary artery bypass grafting/left internal mammary artery (2). There were 7 occlusions and 20 high-grade stenoses. Access was attempted via brachial cutdown (19) or percutaneous puncture of the brachial (2) or femoral arteries (10). Twenty-two lesions were stented with either self-expanding (13) or balloon-expandable (9) stents. Technical success was 89%; 3 occluded lesions could not be crossed owing to complete occlusion. The remaining 4 occlusions were all crossed via a retrograde approach. The mean difference in systolic blood pressure between upper limbs decreased from 36 mm Hg (preprocedure) to 10 mm Hg (postprocedure). There were no procedure-related complications. Mean follow-up was 18 months (range 1–62 months). One patient died 4 months after the procedure secondary to complications from pulmonary surgery unrelated to the percutaneous transluminal angioplasty/stent. Of the 4 successfully treated occlusions, 2 were followed up to 3 years with continued patency. Three patients developed recurrent stenoses documented by duplex examination. However, these patients remained asymptomatic and were not treated. Endovascular management of high-grade lesions of the subclavian or innominate arteries is safe and efficacious and may be considered as a first line of therapy. Continued follow-up is needed to assess long-term patency.
Ortner's Syndrome and Endoluminal Treatment of a Thoracic Aortic Aneurysm
Authors: Escribano Josè F. Guijarro , Carnès Jerûnimo , Crespo Miguel A. Brinquis , Antûn Rafael Fern·ndez
Published: March 2006

Left recurrent laryngeal nerve paralysis was first described in 1897 by Ortner in a patient with mitral valve disease. However, this paralysis has also been attributed to other cardiovascular pathologies, such as thoracic aortic aneurysms. In 1971, Parodi introduced the endoluminal technique by inserting endovascular prostheses for the treatment of vascular aneurysms. The authors present a case of acute dysphonia following left recurrent laryngeal nerve paralysis, confirmed by laryngoscopy, in a patient who was diagnosed with a saccular thoracic aortic aneurysm and treated with endovascular prostheses. It was not necessary to perform any additional surgical procedures on the vocal folds because the patient showed sufficient improvement during speech therapy. Follow-up exams at 3 and 6 months demonstrated the lack of any swallowing or respiratory disorders.
Advances in the Surgical Treatment of Fecal Incontinence
Authors: Person Benjamin , Wexner Steven D.
Published: March 2006

Although surgery for fecal incontinence has been shown to be effective, it is still very challenging and sometimes frustrating. Overlapping sphincteroplasty, by far the most common procedure, is effective in patients with sphincter defects; however, recent data suggest that success rates tend to deteriorate over time. A thorough preoperative evaluation incorporates numerous factors, including patient characteristics, severity of incontinence, type and size of the sphincter defect as assessed by physical examination, anal ultrasound, and anorectal physiology studies including anal manometry, electromyography, and pudendal nerve terminal motor latency assessment. The use of these evaluation methods has allowed better patient assignment for a variety of new alternative treatment options. Innovations in the surgical treatment of fecal incontinence range from simple, office-based sphincter augmentation techniques to surgical implantation of mechanical devices. This article reviews 5 alternative surgical treatment options for fecal incontinence: injection of carbon-coated beads in the submucosa of the anal canal, radiofrequency energy delivery, stimulated graciloplasty, artificial bowel sphincter, and sacral nerve stimulation.
A Short-Term Delayed Approach to Laparoscopic Ventral Hernia When Injury Is Suspected
Authors: Lederman Andrew B. , Ramshaw Bruce J.
Published: March 2006

Laparoscopic repair is a safe and effective method for treating ventral hernias. Although the risk of bowel injury is low, its management is controversial. When injury is suspected or repaired, the risk of infection might prohibit a repair with prosthetic mesh. The timing of safe mesh placement is unclear. We retrospectively reviewed 9 patients from our prospective laparoscopic ventral hernia database who were treated with a 2-to 6-day delay in mesh placement due to violation of the gastrointestinal tract or risk of unidentified or delayed injury. All 9 patients had large ventral hernias from previous laparotomies (average defect, 399.4 cm2) and presented for elective repair. Three of the patients were morbidly obese, and one was diabetic. The decision to delay mesh placement was made intraoperatively. Reasons for delay were colotomy with repair, extensive serosal tears, resection after enterotomy, and resection for chronic small bowel obstruction. All patients received broad-spectrum antibiotics while awaiting definitive repair. In 7 patients, mesh was successfully placed between postoperative days 2 and 6. Delayed mesh placement failed in 2 patients due to loss of domain with bowel edema. The average length of stay was 9 days (range, 6 to 15 days) and average follow-up was 136 days (range, 36 to 303 days). No early mesh infections or other major complications were reported. A short delay of 2 to 6 days with antibiotic coverage is a safe strategy for managing potential or recognized injury to the gastrointestinal tract during laparoscopic ventral hernia repair.
Evidence-Based Practice in Laparoscopic Surgery: Perioperative Care
Authors: Goldfaden Aaron , Birkmeyer John D.
Published: March 2006

Best practices for reducing risks of postoperative infection, venous thromboembolism, and nausea and vomiting in patients undergoing laparoscopic surgery are uncertain. As a result, perioperative care varies widely. We reviewed evidence from randomized clinical trials on the effectiveness of interventions for postoperative infection, venous thromboembolism, and nausea and vomiting Data sources were the Cochrane Central Register of Clinical Trials, reference lists of published trials, and randomized clinical trials published in English since 1990. Trials were also limited to those focused on patients undergoing laparoscopic surgery. Data from 98 randomized clinical trials were included in the final analysis. Routine antibiotic use in laparoscopic cholecystectomy, and possibly other clean procedures not involving placement of prostheses, is likely unnecessary. Similarly, venous thromboembolism prophylaxis is probably unnecessary for low-risk patients undergoing brief procedures. Of a wide variety of methods for reducing postoperative nausea and vomiting, serotonin receptor antagonists appear the most effective and should be considered for routine prophylaxis.
Bariatric Surgery: Assessing Opportunities for Value Innovation
Authors: Tarantino David P. , Smith Darlene B.
Published: March 2006

Obesity has been increasing over the past two decades, and the amount of medical and media attention given to bariatric surgery as a promising option for morbidly obese individuals is growing. The growth of bariatric surgery also has been attributed to improved surgical technique, the increase in surgeons trained in laparoscopic procedures, as well increased public awareness with celebrities haven successfully undergone surgery. The number of surgeons and hospitals offering bariatric services is increasing. How then does a surgeon or a hospital develop a competitive strategy? The first step is to understand the health-care industry. The key forces are rivalry among present competitors, and the bargaining power of suppliers and buyers. While bariatric surgery currently is in a growth phase, time and competition will force practitioners to compete on the basis of price, unless they find true competitive advantage. Value innovation, is a means of creating new marketing space by looking across the conventionally defined boundaries of business-across substitute industries, across strategic groups, across buyer groups, across complementary product and service offerings, and across the functionalemotional orientation of an industry. One can compete by offering similar services focusing primarily on cost efficiencies as the key to profitability. Alternatively, one can break free from the pack by innovating and focusing on delivering superior value to the customer. As the market for bariatric surgery becomes increasingly overcrowded, profitable growth is not sustainable without developing a clear differential advantage in the market. Value innovation allows you to develop that advantage.
Applications of Fibrin Sealant in Surgery
Authors: Lee Meng-G Martin , Jones Daniel
Published: March 2006

Fibrin sealant has been used with increasing frequency in a variety of surgical field for its unique hemostatic and adhesive abilities. Fibrin sealant mimics the last step of the coagulation cascade and takes place independently of the patient's coagulation status. With rapid advances in minimally invasive surgery, the potential uses for this type of biologic and synthetic material are expanding exponentially. This article reviews the data associated with the application of fibrin sealant in various surgical procedures. From reinforcing gastrointestinal anastomosis to repair perforated duodenal ulcers to mesh fixation in laparoscopic inguinal hernia repair, fibrin sealant is gaining increasing acceptance among surgeons. The applications of fibrin sealant are expanding, and new preparations of fibrin sealant are currently being evaluated.
Small Bowel Transit Does Not Correlate With Outcome of Surgery in Patients With Colonic Inertia
Authors: Zmora Oded , Colquhoun Patrick , Katz Joshua , Efron Jonathan , Weiss Eric G. , Nogueras Juan J. , Vernava Anthony M. , Wexner Steven D.
Published: March 2006

Colonic inertia is a motility disorder that may involve dysfunction of the entire intestinal tract. The aim of this study was to assess whether small bowel transit time is associated with the outcome of total abdominal colectomy in patients with colonic inertia. A retrospective review of the medical records of patients who underwent total abdominal colectomy for colonic inertia was performed to identify those individuals who had a preoperative small bowel transit study. The outcome of surgery was correlated with the results of the small bowel transit study. Fifty-two female patients underwent total abdominal colectomy for colonic inertia between 1988 and 2000, of whom 17 (33%) had a preoperative small bowel transit study. The small bowel transit time was normal in 11 patients (65%), and the time was abnormally prolonged in 6 (35%). At a mean follow-up of 37 months, there was no significant difference in the outcome of surgery between the two groups. A good result was achieved in 36% of the normal small bowel transit time group compared with 33% in the abnormal group; the result was fair in 63% and 33%, and poor in 0% and 33%, respectively (P= NS). The small bowel transit study does not reliably predict the outcome of total abdominal colectomy in patients with colonic inertia.
Oxidative Damage in an Experimentally Induced Gastric and Gastroduodenal Reflux Model
Authors: Erbil Yesim , Türkoglu Umit , Barbaros Umut , Balik Emre , Olgac Vakur , Kaya Hakan , Cimşit Bayindir
Published: March 2006

The exact pathophysiologic mechanisms of esophageal cell damage and carcinogenesis by gastroesophageal reflux are not clearly understood. The aim of this study was to evaluate the damage to the esophageal epithelium that occurs after acid reflex and mixed acid and bile reflux by assessing histopathology, reactive oxygen species, and DNA damage. Eighty 10-week-old male Sprague-Dawley rats were divided into two groups, an acid reflux group and a mixed (acid/bile) reflux group. Acid reflux was achieved by esophagogastroplasty in which mixed reflux was encouraged via esophagoduodenal anastomosis. Each group contained a control subgroup that underwent sham laparotomy alone. The rats were killed 3, 6, 9, and 12 months after surgery. Malondialdehyde, protein carbonyl content, and DNA damage were determined in lymphocytes. Histopathologic analysis was performed according to the histologic activity index. Inflammation, ulcer, and regeneration in both reflux groups were significantly increased in the esophagus at 3, 6, 9, and 12 months compared with the control group. Mucosal damage was greater in the mixed reflux group compared with the gastric reflux group. Malondialdehyde and carbonyl content in the serum, and DNA damage in lymphocytes, were significantly increased in both reflux groups. At 9 and 12 months, oxidative damage was increased in the mixed reflux group compared with the acid reflux group. Oxygen-derived free radicals seem to be one of the important mediators in the evaluation and generation of reflux esophagitis. The impact of oxygen free radicals, as demonstrated in this study, can be evaluated by assessing the damage that they incur to lipid membranes, serum proteins, and circulating lymphocyte DNA. Serum malondialdehyde and carbonyl content as well as lymphocyte DNA damage were significantly increased in the setting of acid and mixed acid/bile reflux in these rodent models. Further, these serum and lymphocytic changes were associated with esophageal ulceration, inflammation, and regeneration. Evaluation of such markers as serum malondialdehyde and carbonyl content as well as evaluation of lymphocyte DNA might prove to be useful investigations in patients with precancerous and cancerous conditions in addition to conventional methods of diagnosis. Further studies, both animal and human are warranted.
Small Intestinal Submucosa Intracardiac Patch: An Experimental Study
Authors: Rosen Michael , Roselli Eric E. , Faber Cristiano , Ratliff Norman B. , Ponsky Jeffrey L. , Smedira Nicholas G.
Published: March 2006

In this experimental study, small intestinal submucosa was implanted as an atrial prosthesis in calves. Echocardiography and histology showed this to be an impermeable prosthesis that develops a neointimal nonthrombogenic surface making it safe for repair of defects in a low-pressure system. Further study with small intestinal submucosa in an intracardiac position is warranted.
Minimally Invasive: Minimally Reimbursed? An Examination of Six Laparoscopic Surgical Procedures
Authors: Roumm Adam R. , Pizzi Laura , Goldfarb Neil I. , Cohn Herbert
Published: March 2006

It is generally believed that minimally invasive surgery (MIS) results in less postoperative pain, fewer complications, and shorter recovery periods compared with open procedures. Yet despite these benefits, the level of reimbursement assigned to the surgeon by United States health-care payers is often lower than that for open procedures. Furthermore, the cost of performing a MIS may be higher vs an open procedure because specialized equipment, increased surgical time, or both may be required. In this report, we examine the issue by comparing reimbursements for MIS with open procedures, summarizing the medical literature on MIS vs open surgical procedures, and offering recommendations for payers who establish reimbursement policies. The review is focused on six MIS procedures where outcomes data exist: laparoscopic cholecystectomy (lap chole), laparoscopic colectomy (LC), laparoscopic fundoplication (LF), laparoscopic hysterectomy (LH), laparoscopic ventral hernia repair (LVHR), and laparoscopic appendectomy (LA). Outcomes summarized were length of hospital stay (LOS), operating room time, operating room costs, complications, and return to work or normal activities. The level of scientific evidence was assigned to each study using predetermined criteria. A total of 112 articles were reviewed: 14 for lap chole, 26 for LC, 7 for LF, 19 for LH, 9 for LVHR, and 37 for LA. The data demonstrate that these procedures result in reduced hospital stay, reduced hospital costs, and faster return to work or normal activities. Yet, the operating room time and costs are frequently higher for MIS. These findings suggest that as both the outcomes value and level of operating room resources are greater, MIS warrants reimbursement that meets or exceeds that of open procedures.
Clinical Presentation and Surgical Outcome in Patients With Solitary Rectal Ulcer Syndrome
Authors: Choi Hong Jo , Shin Eung Jin , Hwang Yong Hee , Weiss Eric G. , Nogueras Juan J. , Wexner Steven D.
Published: March 2006

Solitary rectal ulcer syndrome is a poorly understood clinical condition, and the schema of treatment has not yet been defined. This study reviewed the clinical spectra and outcome of various surgical treatments in patients with solitary rectal ulcer syndrome. The medical records of all patients with solitary rectal ulcer syndrome between 1992 and 1998 were retrospectively reviewed. Patients in the study population with symptoms and histopathologic findings suggestive of solitary rectal ulcer syndrome were placed in the primary solitary rectal ulcer syndrome group, and patients who underwent surgery for other diseases in whom histopathology confirmed concomitant solitary rectal ulcer syndrome were in the incidental group. Clinical features and outcomes of surgical treatment were documented. Improvement was considered as resolution of presenting symptoms, and nonimprovement was considered if presenting symptoms persisted or worsened. The study cohort comprised 49 patients: 20 in the primary group and 29 in the incidental group. Ulcerative morphology was seen predominantly in the primary group (70%); erythematous (45%) and polypoid lesions (34%) were predominant in the incidental group (P= .0025). Clinical improvement after surgery was seen in 74% of patients with primary and 79% with incidental solitary rectal ulcer syndrome (P= NS). Manifestations such as tenesmus and digitation correlated with poorer outcome after surgery in both groups. Solitary rectal ulcer syndrome is a clinical condition associated with functional anorectal evacuatory disorders. The results of this study show the positive role of surgical treatment for underlying functional disorders in the improvement of incidental solitary rectal ulcer syndrome.
The Steinberg-Bernstein Centre for Minimally Invasive Surgery at McGill University
Authors: Fried Gerald M.
Published: March 2006

Surgical skills and simulation centers have been developed in recent years to meet the educational needs of practicing surgeons, residents, and students. The rapid pace of innovation in surgical procedures and technology, as well as the overarching desire to enhance patient safety, have driven the development of simulation technology and new paradigms for surgical education. McGill University has implemented an innovative approach to surgical education in the field of minimally invasive surgery. The goal is to measure surgical performance in the operating room using practical, reliable, and valid metrics, which allow the educational needs of the learner to be established and enable feedback and performance to be tracked over time. The GOALS system and the MISTELS program have been developed to measure operative performance and minimally invasive surgical technical skills in the inanimate skills lab, respectively. The MISTELS laparoscopic simulationtraining program has been incorporated as the manual skills education and evaluation component of the Fundamentals of Laparoscopic Surgery program distributed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the American College of Surgeons.
Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice
Authors: Lee Byeong-Chel , Avraham Shalom , Imamoto Akira , Avraham Hava Karsenty
Published: March 2006

Matk/CHK knockout mice were reported to show no apparent phenotypic abnormalities. This was thought to be due to the homologous kinase Csk that compensates for Matk/CHK. Here, we present the first evidence that the nonreceptor tyrosine kinase, Matk/CHK, is an important modulator of immune cell signaling. We found that the frequency of primitive hematopoietic cells, the side population c-kit+ Lin– Sca-1+ (SPKLS) cells, in Matk/CHK–/– mice was increased 2.2-fold compared with the control mice. Moreover, Matk/CHK deficiency led to significantly higher pre–B cell colony formation following IL-7 stimulation. Interestingly, when mice received the in vivo antigen challenge of TNP-ovalbumin followed by restimulation, the Matk/CHK–/– lymph node and spleen cells produced significantly lower IFN-γ levels compared with the respective wild-type cells. Our study indicates that Matk/CHK is not functionally redundant with Csk, and that this tyrosine kinase plays an important role as a regulator of immunologic responses.
Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes
Authors: Ogata Kiyoyuki , Kishikawa Yoshifumi , Satoh Chikako , Tamura Hideto , Dan Kazuo , Hayashi Akio
Published: March 2006

The diagnosis of myelodysplastic syndromes (MDS) without an increase in blasts and ringed sideroblasts (low-grade MDS without ringed sideroblasts [LGw/oRS]) may be problematic because dysplastic features are not specific to MDS and approximately 50% of patients with LGw/oRS lack chromosomal aberrations. Here, we report the usefulness of flow cytometric characteristics of CD34+ cells for LGw/oRS diagnosis. Bone marrow cells from LGw/oRS patients and controls (eg, cytopenic individuals without MDS) were analyzed using 4-color flow cytometry (FCM). We objectively determined reference ranges of 13 parameters related to CD34+ cells with data from controls. In LGw/oRS patients, various abnormalities of CD34+ cells—eg, decrease in CD34+ B-cell precursors, aberrant expression or overexpression of various antigens on CD34+ myeloblasts—were observed. We constructed a reproducible, flow cytometric scoring system for LGw/oRS diagnosis. High scores were observed in 16 of 27 LGw/oRS patients, regardless of the presence or absence of chromosomal aberrations, but not in any of the 90 controls. Among LGw/oRS patients with chromosomal aberrations, patients with trisomy 8 or del20(q) had low FCM scores (P = .002). As a result, most LGw/oRS patients were identified based on high FCM score, chromosomal aberration, or both.
Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia
Authors: Rudd Matthew F. , Sellick Gabrielle S. , Webb Emily L. , Catovsky Daniel , Houlston Richard S.
Published: March 2006

We conducted a large-scale association study to identify low-penetrance susceptibility alleles for chronic lymphocytic leukemia (CLL), analyzing 992 patients and 2707 healthy controls. To increase the likelihood of identifying disease-causing alleles we genotyped 1467 coding nonsynonymous single nucleotide polymorphisms (nsSNPs) in 865 candidate cancer genes, biasing nsSNP selection toward those predicted to be deleterious. Preeminent associations were identified in SNPs mapping to genes pivotal in the DNA damage-response and cell-cycle pathways, including ATM F858L (odds ratio [OR] = 2.28, P < .0001) and P1054R (OR = 1.68, P = .0006), CHEK2 I157T (OR = 14.83, P = .0008), BRCA2 N372H (OR = 1.45, P = .0032), and BUB1B Q349R (OR = 1.42, P = .0038). Our findings implicate variants in the ATM-BRCA2-CHEK2 DNA damage-response axis with risk of CLL.
Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is not linked to glucocorticoid resistance in childhood ALL
Authors: Tissing Wim J. E. , Meijerink Jules P. P. , Brinkhof Bas , Broekhuis Mathilde J. C. , Menezes Renee X. , den Boer Monique L. , Pieters Rob
Published: March 2006

Glucocorticoid (GC) resistance is an adverse prognostic factor in childhood acute lymphoblastic leukemia (ALL), but little is known about causes of GC resistance. Up-regulation of the glucocorticoid receptor (GR) has been suggested as an essential step to the induction of apoptosis in leukemic cells. In this study we investigated whether baseline mRNA expression levels of the 5 different GR promoter transcripts (1A1, 1A2, 1A3, 1B, and 1C) or differences in the degree of regulation of the GR or GR promoter transcripts upon GC exposure are related to GC resistance. Therefore, mRNA levels of the 5 GR promoter transcripts and of the GR were measured by quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR; Taqman) technology in primary ALL cells prior to and after 3, 8, and 24 hours of prednisolone exposure. GR expression is induced upon GC exposure in primary ALL patient samples, which is opposite to what is found in tissues in which GCs do not induce apoptosis. GC resistance in childhood ALL cannot be attributed to an inability of resistant cells to up-regulate the expression of the GR upon GC exposure, nor to differences in GR promoter usage (at baseline and upon GC exposure).
Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-κB (NF-κB), pyrrolidine dithiocarbamate
Authors: Kitamei Hirokuni , Iwabuchi Kazuya , Namba Kenichi , Yoshida Kazuhiko , Yanagawa Yoshiki , Kitaichi Nobuyoshi , Kitamura Mizuki , Ohno Shigeaki , Onoé Kazunori
Published: March 2006

Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-κB (NF-κB), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor α and interleukin-1β were suppressed in eyes of PDTC-treated EAU mice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-κB pathway in the lesion could be a novel target for the successful control of uveoretinitis.
On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by human neutrophils
Authors: Cassatella Marco A
Published: March 2006

Contrary to their traditional characterization as terminally differentiated effectors of inflammation, neutrophils are remarkably versatile cells. Indeed, their capacity to change phenotype under specific circumstances, their active involvement in the regulation and resolution of inflammation, their response to a wide variety of cytokines and chemotactic molecules, and their regulatory role in angiogenesis and tumor fate have made it clear that they represent far more than “short-lived cells devoid of transcriptional activities, that only release preformed mediators and kill pathogens”. The multiple and amazing functional capacities of this cell type are also illustrated by the fact that the neutrophil may function as an important source of cytokines, at levels comparable with and in some cases, higher than those made by other leukocytes. To date, the families of cytokines, which in vitro or in vivo have been convincingly reported as being produced by neutrophils, include proinflammatory/anti-inflammatory cytokines, immunoregulatory cytokines, chemokines, angiogenic/fibrogenic factors, and tumor necrosis factor (TNF) superfamily members. The latter molecules are multifaceted cytokines whose integrated actions not only influence the development, homeostasis, and adaptive responses of many cells and tissue types but are also implicated in the antitumoral response. The recent findings that neutrophils produce in a finely regulated manner a TNF superfamily member involved in tumor cell killing and autoimmunity, namely TNF-related apoptosis-inducing ligand, open an additional perspective to exploit neutrophils for novel roles in anticancer responses and modulation of autoimmune diseases.
Naltrexone inhibits alcohol-mediated enhancement of HIV infection of T lymphocytes
Authors: Wang Xu , Douglas Steven D , Peng Jin-Song , Metzger David S , O’Brien Charles P , Zhang Ting , Ho Wen-Zhe
Published: March 2006

Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific μ-opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7 (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous β-endorphin production and induced μ-opioid receptor mRNA expression in PBL and CEMX174 cells. The role of β-endorphin in alcohol-mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol- or exogenous β-endorphin-mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV-infected alcoholics.
Patient preference randomised controlled trials in mental health research
Authors: Howard Louise , Thornicroft Graham
Published: March 2006

The relationship between psychiatric patients' preferences for different treatments and the outcome of interventions is unclear, as the few relevant trials have tended to be underpowered. Strong patient preferences result in patients refusing to enter a trial. This leads to bias and limits generalisability, and the patient preference randomised controlled trial (RCT) design has been proposed as an alternative. Limitations and advantages of patient preference RCTs are discussed.
Duloxetine in the prevention of relapse of major depressive disorder
Authors: Perahia David G. , Gilaberte Inmaculada , Wang Fujun , Wiltse Curtis G. , Huckins Stacy A. , Clemens Jeffrey W. , Montgomery Stuart A. , Montejo Angel L. , Detke Michael J.
Published: March 2006

Background

Relapse rates may be as high as 50% in people with major depressive disorder (MDD) previously treated to remission.

Aims

Duloxetine, an inhibitor of serotonin and noradrenaline reuptake that is licensed in Europe, the USA and elsewhere for the treatment of depressive episodes, was evaluated with regard to its efficacy, safety and tolerability in the prevention of relapse of MDD.

Method

Adult out-patients with MDD received duloxetine (60 mg daily) for 12 weeks (n=533). Patients who responded to the drug were then randomised to duloxetine (60 mgdaily) (n=136) or placebo (n=142) for 26 weeks. The primary measure of efficacy was time to relapse.

Results

Patients who received duloxetine (60 mg daily) experienced significantly longer times to relapse of MDD, and better efficacy global well-being, and quality-of-life outcomes compared with patients who received placebo. It should be noted that adverse events which occur in discontinuation may mimic some signs of depressive relapse, and were not specifically elicited in this study.

Conclusions

Duloxetine (60 mg daily) is effective in the prevention of relapse of MDD during continuation treatment.
Emergency psychiatry, compulsory admissions and clinical presentation among immigrants to the Netherlands
Authors: Mulder Cornelis L. , Koopmans Gerrit T. , Selten Jean-Paul
Published: March 2006

Background

Black individuals in the UK have higher rates of contact with psychiatric emergency services than their White counterparts. It is unknown whether this is also the case in other European countries.

Aims

To compare the risk of contact with psychiatric emergency services and of compulsory admission between immigrant groups to The Netherlands and Dutch natives, and to determine the unique contribution of ethnicity to compulsory admission.

Method

Study of 720 people referred to emergency psychiatric services in Greater Rotterdam, The Netherlands.

Results

The relative risks (RRs) for contacts with psychiatric emergency services, for having a psychotic disorder and for compulsory admission were significantly higher in most immigrant groups. Moroccans, Surinamese and Dutch Antilleans had the highest risks of compulsory admission. After controlling for symptom severity, danger, motivation for treatment and level of social functioning, non-Western origin was no longer associated with compulsory admission.

Conclusions

Non-Western immigrant groups were overrepresented in psychiatric emergency care and were admitted compulsorily more frequently, possibly owing to a different clinical presentation.
Validation and development of a self-report outcome measure (MAP-sc) in opiate addiction
Authors: Luty Jason , Perry Vincent , Umoh Oken , Gormer Donna
Published: March 2006

Aims and Method

To develop and assess the viability of a self-completion version of the Maudsley Addiction Profile for assessing and monitoring the functioning of opioid-dependent patients. A total of 206 treatment-seeking opioid-dependent patients completed the Maudsley Addiction Profile interview and a self-completion version at a single clinic appointment at a substance misuse facility. Scores from both formats were compared using correlation coefficients.

Results

Non-parametric correlation coefficients between interview and self-completion version for alcohol, drug, psychiatric, family and legal problems correlated in excess of 0.7 for the majority of the 20 items that were compared.

Clinical Implications

A short, self-administered questionnaire version of the Maudsley Addiction Profile is a feasible alternative to the interview for assessing and monitoring treatment of opioid-dependent patients. The questionnaires were usually completed by clients within 15 min. These would be particularly useful in services with very limited staffing time, such as primary care.
Examining the concept of patient satisfaction in patients with a diagnosis of schizophrenia: a qualitative study
Authors: Duggins Richard , Shaw Ian
Published: March 2006

Aims and Method

Ten people with a diagnosis of schizophrenia were interviewed. The interviews were analysed qualitatively with the aim of examining the concept of patient satisfaction in the context of a recent in-patient admission.

Results

The analysis identified two themes that influenced the expression of patient satisfaction: external factors and internal factors. The theme of external factors contained four categories: fear of violence, communication with staff, lack of autonomy and ward routines. The theme of internal factors comprised participants' conceptions and expectations.

Clinical Implications

This small study suggests the complexity of the concept of patient satisfaction should be respected in assessing experiences of people with a diagnosis of schizophrenia.
E-Mental health in Pakistan: a pilot study of training and supervision in child psychiatry using the internet
Authors: Rahman Atif , Nizami Asad , Minhas Aisha , Niazi Rashda , Slatch Munir , Minhas Fareed
Published: March 2006

The ‘brain drain’, resulting from the recruitment by the UK of highly qualified mental health professionals from middle- and low-income countries, has been described as a serious problem effecting the service provision, training and research capacity of these countries (Doku & Mallett, 2003; Thara et al, 2004). Although this issue is important, the benefits of such migration are seldom highlighted. Professionals who migrate often invest in families and businesses in their home country and are a source of valuable foreign income. Many professionals undergo specialised training and gain experience not available in their home countries and then return to provide an enhanced level of service (Tareen, 2000). Such movement may also serve a catalytic purpose. An example of a sector that has gained enormously from the so-called brain drain is information technology in India, which is built largely around expatriates in the USA and their networks back home. The high profile of Indian information technology experts has encouraged a whole new generation to pursue excellence in this field.
Evaluation of an Alternate Dosing Strategy for Cisplatin in Patients With Extreme Body Surface Area Values
Authors: Loos Walter J. , de Jongh Felix E. , Sparreboom Alex , de Wit Ronald , van Boven-van Zomeren Desiree M. , Stoter Gerrit , Nooter Kees , Verweij Jaap
Published: March 2006

Purpose

The majority of cytotoxic drugs for adults are dosed based on body surface area (BSA), aiming to reduce interpatient variability in drug exposure. We prospectively studied the usefulness of BSA-based dosing of cisplatin in patients at extremes of BSA values.

Patients and Methods

Patients were randomly assigned to receive a fixed dose of cisplatin in course 1, and a BSA-adjusted dose in course 2, or vice versa. The fixed dose was based on the average BSA for males and females, while extremes were set at BSA values exceeding the average ± 1 standard deviation. Subsequently, we retrospectively analyzed data from a normal population.

Results

In 25 patients assessable for both courses, the use of a fixed dose of cisplatin resulted in reduced exposure to unbound platinum in patients at the upper extremes of BSA (P = .003) and higher exposures in patients at the lower extremes (P = .009), as compared with exposures following the BSA-adjusted dose. Although clearance was related to BSA (R2 = 0.44; P < .001), only a small reduction in interpatient variability in clearance after correction for BSA was achieved (20.8% v 17.1%). In the retrospective analysis, compared with the average patient, the clearance of unbound platinum in patients with a BSA value ≤ 1.65 m2 was 16% slower (P < .001), while an 18% faster clearance (P < .001) was observed in patients with a BSA value ≥ 2.05 m2.

Conclusion

Unless better predictors for platinum clearance are identified, fixed-dose regimens per BSA cluster (≤ 1.65 m2; 1.66 m2 to 2.04 m2; ≥ 2.05 m2) are recommended.
Improvement of Overall and Failure-Free Survival in Stage IV Follicular Lymphoma: 25 Years of Treatment Experience at The University of Texas M.D. Anderson Cancer Center
Authors: Liu Qi , Fayad Luis , Cabanillas Fernando , Hagemeister Fredrick B. , Ayers Gregory D. , Hess Mark , Romaguera Jorge , Rodriguez M. Alma , Tsimberidou Apostolia M. , Verstovsek Srdan , Younes Anas , Pro Barbara , Lee Ming-Sheng , Ayala Ana , McLaughlin Peter
Published: March 2006

Purpose

Advanced-stage follicular lymphoma is considered incurable. The pace of improvements in treatment has been slow. This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002.

Methods

Five consecutive studies (two were randomized trials) involving 580 patients were analyzed for overall survival (OS), failure-free survival (FFS), and survival after first relapse. A proportional hazards analysis, and subset analyses using the follicular lymphoma international prognostic index (FLIPI) score were performed. Treatment regimens included: cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin (CHOP-Bleo); CHOP-Bleo followed by interferon alfa (IFN-α); a rotation of three regimens (alternating triple therapy), followed by IFN-α; fludarabine, mitoxantrone, dexamethasone (FND) followed by IFN-α; and FND plus delayed versus concurrent rituximab followed by IFN-α.

Results

Improvements in 5-year OS (from 64% to 95%) and FFS (from 29% to 60%) indicate steady progress, perhaps partly due to more effective salvage therapies, but the FFS data also indicate improved front-line therapies; these observations held true after controlling for differences in prognostic factors among the cohorts. The FLIPI model adds rigor to and facilitates comparisons among the different cohorts. An unexpected finding in this study was a trend toward an apparent FFS plateau.

Conclusion

Evolving therapy, including the incorporation of biologic agents, has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma. The apparent plateau in the FFS curve, starting approximately 8 to 10 years from the beginning of treatment, raises the issue of the potential curability of these patients.
Phase III Intergroup Study of Fludarabine Phosphate Compared With Cyclophosphamide, Vincristine, and Prednisone Chemotherapy in Newly Diagnosed Patients With Stage III and IV Low-Grade Malignant Non-Hodgkin's Lymphoma
Authors: Hagenbeek Anton , Eghbali Houchingue , Monfardini Silvio , Vitolo Umberto , Hoskin Peter J. , de Wolf-Peeters Christiane , MacLennan Ken , Staab-Renner Elvira , Kalmus Joachim , Schott Astrid , Teodorovic Ivana , Negrouk Anastassia , van Glabbeke Martine , Marcus Robert
Published: March 2006

Purpose

To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study.

Patients and Methods

Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks).

Results

Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients.

Conclusion

Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.
Peripheral Neuropathy Induced by Microtubule-Stabilizing Agents
Authors: Lee James J. , Swain Sandra M.
Published: March 2006

Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones, are effective chemotherapeutic agents for the treatment of many cancers. Neuropathy is a major adverse effect of MTSA-based chemotherapy, with severe peripheral neuropathy (grade 3 or 4) occurring in as many as 30% of patients treated with a MTSA. MTSA-induced neuropathy usually resolves gradually after cessation of the treatment. The most reliable method to accurately assess MTSA-induced neuropathy is by clinical evaluation, although additional techniques are being developed and evaluated. Among MTSA-induced neuropathy, the most extensively studied is that induced by taxanes; such a neuropathy usually presents as sensory neuropathy and is more common with paclitaxel than docetaxel. The incidence of MTSA-induced neuropathy seems to depend on the MTSA dose per treatment cycle, the schedule of treatment, and the duration of the infusion. Although there have been several small clinical trials with neuroprotective agents, early recognition and supportive care are the best approaches for prevention and management of MTSA-induced neuropathy. In the future, research should focus on elucidating the mechanism of MTSA-induced neuropathy, developing reliable in vivo and in vitro preclinical models to study MTSA-induced neuropathy, developing a more reliable grading system for MTSA-induced neuropathy, developing more reliable methods for evaluating MTSA-induced neuropathy, and evaluating the efficacy of potential neuroprotective agents in clinical trials.