bluuebunny/crossref_metadata_2025 huggingface dataset:
Onlay Hiatal Reinforcement Utilizing Human Acellular Dermal Matrix: Three Case Series
Authors: Johnson Jason M. , Carmody Brennan J. , Jamal Mohammad K. , Demaria Eric J.
Published: March 2006

Redo laparoscopic fundoplication and laparoscopic repair of large (> 5cm) paraesophageal hernias have a high rate of recurrence after primary suture repair of the hiatal defect. As such, the use of mesh prosthesis as an interposition graft or onlay reinforcement is becoming more popular for the repair of larger, more complicated crural defects. We report three cases in which human acellular dermal matrix was used as an onlay reinforcement of the hiatus after primary suture closure. Two patients had large paraesophageal hernias (one type III and one type IV). The third patient became symptomatic after her second laparoscopic antireflux procedure and was found to have recurrent herniation of the fundus into the mediastinum. All three patients underwent successful laparoscopic repair. There were no intraoperative or postoperative complications. All three patients remain symptom free with follow-up ranging from 8 months to 10 months. Acellular dermal matrix appears to be a promising prosthetic for onlay reinforcement of the hiatus during redo laparoscopic fundoplication and repair of large paraesophageal hernias.
Short-Term Health-Related Quality of Life After Abdominal Surgery: A Conceptual Framework
Authors: Urbach David R. , Harnish Julie L. , Long Gina
Published: March 2006

We sought to develop a conceptual framework of health-related quality of life (QOL) after abdominal surgery to assist in the development of a QOL measure suitable for use in clinical trials comparing laparoscopic and conventional surgery. We conducted semi-structured interviews with 21 patients within 2 weeks after an abdominal surgical procedure. Responses were transferred into an electronic spreadsheet and coded to facilitate analysis. We tabulated the frequency of similar responses and grouped response items into areas of QOL impairment. The patients ranged in age from 19 to 78 years. Six had laparoscopic procedures. Patients identified the following areas of QOL impairment (examples of specific items and frequency of response): (1) physical limitations (difficulty getting in and out of bed 52%, difficulty walking 48%), (2) functional impairment (inability to perform usual activities 100%, difficulty bathing 90%), (3) pain (pain in incision 48%, pain with coughing or movement 28%), (4) visceral function (inability to eat 48%, lack of appetite 43%), (5) sleep (frequent nighttime awakening 62%, difficulty falling asleep 33%), and (6) mood (helplessness 28%, anxiety 24%). Acute health status after abdominal surgery constitutes a unique, dynamic health state characterized by impairment in a number of different health domains. A measure of QOL after abdominal surgery should have adequate coverage of these health concepts.
The Southwestern Center for Minimally Invasive Surgery
Authors: Watson Mark Jay , Tesfay Seifu T.
Published: March 2006

As the 80-hour work week impacts training that occurs in the operating room, and as Residency Review Committees seek evidence of how skills are taught, there is a need to focus on innovative strategies and methodologies that are being employed. This section on Surgical Education will periodically highlight Surgical Skills Centers, their experiences in training, and new technology. We welcome the opportunity to share the innovative work that you are doing. If you would like to have your center showcased, please contact Dr Kimberly Anderson at .
Automatic Detection and Notification of “Wrong Patient—Wrong Location” Errors in the Operating Room
Authors: Sandberg Warren S. , Häkkinen Matti , Egan Marie , Curran Paige K. , Fairbrother Pamela , Choquette Ken , Daily Bethany , Sarkka Jukka-Pekka , Rattner David
Published: March 2006

When procedures and processes to assure patient location based on human performance do not work as expected, patients are brought incrementally closer to a possible “wrong patient—wrong procedure” error. We developed a system for automated patient location monitoring and management. Realtime data from an active infrared/radio frequency identification tracking system provides patient location data that are robust and can be compared with an “expected process” model to automatically flag wrong-location events as soon as they occur. The system also generates messages that are automatically sent to process managers via the hospital paging system, thus creating an active alerting function to annunciate errors. We deployed the system to detect and annunciate “patientin-wrong-OR” events. The system detected all “ wrongoperating room (OR)” events, and all “wrong-OR” locations were correctly assigned within 0.50 ± 0.28 minutes (mean ± SD). This corresponded to the measured latency of the tracking system. All wrong-OR events were correctly annunciated via the paging function. This experiment demonstrates that current technology can automatically collect sufficient data to remotely monitor patient flow through a hospital, provide decision support based on predefined rules, and automatically notify stakeholders of errors.
Surgery in Rural America
Authors: Finlayson Samuel R.G.
Published: March 2006

Despite recent increased attention to ailing health-care systems in rural America, policy makers have paid relatively little attention to the status of rural surgery. This paucity of attention is rooted in a combination of poor communication and incomplete knowledge. Unfortunately, the scarce dialogue between advocates of rural surgery and policy makers has been driven largely by anecdotes and generalizations. What is needed as a foundation for productive discourse is evidence-based objective observations regarding important issues and concerns related to rural surgical practice. This article reviews our current understanding of several of these issues; namely, the adequacy of the current and future surgical workforce, preparation for rural practice, professional isolation, rural surgical quality, and the critical interplay between rural surgeons and local systems of care in which they function. The intent of this article is to stimulate further inquiry that will create a foundation for meaningful dialogue between rural surgeons, surgical leaders, and health-care policy makers
Efficacy of Novel Robotic Camera vs a Standard Laparoscopic Camera
Authors: Strong Vivian E.M. , Hogle Nancy J. , Fowler Dennis L.
Published: March 2006

To improve visualization during minimal access surgery, a novel robotic camera has been developed. The prototype camera is totally insertable, has 5° of freedom, and is remotely controlled. This study compared the performance of laparoscopic surgeons using both a laparoscope and the robotic camera. The MISTELS (McGill Inanimate System for the Training and Evaluation of Laparoscopic Skill) tasks were used to test six laparoscopic fellows and attending surgeons. Half the surgeons used the laparoscope first and half used the robotic camera first. Total scores from the MISTELS sessions in which the laparoscope was used were compared with the sessions in which the robotic camera was used and then analyzed with a paired t test (P< .05 was considered significant). All six surgeons tested showed no significant difference in their MISTELS task performance on the robotic camera compared with the standard laparoscopic camera. The mean MISTELS score of 963 for all subjects who used a laparoscope and camera was not significantly different than the mean score of 904 for the robotic camera (P= .17). This new robotic camera prototype allows for equivalent performance on a validated laparoscopic assessment tool when compared with performance using a standard laparoscope.
Significant Reduction of Laparotomy-Associated Lung Metastases and Subcutaneous Tumors After Perioperative Immunomodulation with Flt3 Ligand in Mice
Authors: Carter Joseph J. , Feingold Daniel L. , Wildbrett Peer , Oh Anthony , Kirman Irena , Asi Zishan , Stapleton George , Huang Emina , Fine Robert L. , Whelan Richard L.
Published: March 2006

Laparotomy has been associated with increased rates of tumor establishment and metastasis formation postoperatively in animal models. The purpose of this study was to determine the impact on postoperative tumor growth of perioperative upregulation of immune function via fetal liver tyrosine kinase 3 (Flt3 ligand). Two murine studies were carried out: the first utilized a lung metastases model, and the second involved a subcutaneous tumor model. Each study included four groups: anesthesia control (AC), AC plus Flt3 ligand (ACFlt3), sham laparotomy (OP), and OP plus Flt3 ligand (OPFlt3). Flt3 ligand was administered by daily intraperitoneal injection (10 µg/dose) beginning 5 days preoperatively and continuing for 1 week postoperatively. In study 1, A/J mice were given tail vein injections of 1.5 x 105 TA3Ha cancer cells on the day of surgery. The mice were sacrificed 14 days after surgery, the lungs processed, and the surface metastases counted by a blinded observer. In study 2 C3H/He mice were given a dorsal subcutaneous injection of 104 MC-2 cancer cells on the day of surgery. The mice were sacrificed 31 days after surgery, and the injection sites were evaluated for subcutaneous tumors grossly and histologically. In study 1, the median number of surface lung metastases per mouse was 166 in the OP group and 38 in the OPFlt3 (P= .021). Mice in the AC group developed a median 50 lung metastases per animal compared with mice in the ACFlt3 group who had a median of 10 metastases per mouse (P= .001). The OP group had significantly more metastases than the AC group (P= .048). In study 2, the percentage of animals that developed tumors in the AC, OP, ACFlt3, and OPFlt3 groups was 43, 80, 0, and 20, respectively. The incidence of tumors in the OPFLt3 group and the ACFlt3 group was significantly less than their respective control groups (P< .01). The difference between the OP and AC groups was not significant (P> .05). Perioperatively administered Flt3 ligand was associated with significantly fewer lung metastases and a lower incidence of subcutaneous tumor formation after laparotomy and anesthesia alone. Perioperative immunomodulation may limit untoward surgery-related oncologic effects.
Telementoring: An Important Enabling Tool for the Community Surgeon
Authors: Sebajang Herawaty , Trudeau Patrick , Dougall Al , Hegge Susan , McKinley Craig , Anvari Mehran
Published: March 2006

This study evaluated the efficacy of telementoring as an enabling tool for community general surgeons to perform advanced laparoscopic surgical procedures. We present a series of 19 patients who underwent advanced laparoscopic surgical procedures in two community hospitals, between November 2002 and July 2003, by four community surgeons with no formal advanced laparoscopic training. Each surgeon was telementored by an expert surgeon from a tertiary care hospital. Telementoring was achieved with real-time two-way audiovideo communications over Internet Protocol or Integrated Services Digital Network lines with bandwidths from 385 kbps to 1.2 mbps. The procedures included 10 bowel resections, 5 Nissen fundoplications, 2 splenectomies, 1 reversal of a Hartmann procedure, and 1 ventral hernia repair. Two of the 19 procedures (11%) were converted to open. There were no intraoperative complications and two postoperative complications (11%). The primary surgeon considered telementoring useful in all cases (median score, 4 of 5). The mentor was also comfortable with the quality of the laparoscopic surgery performed (median score, 4 of 5). Telecommunication bandwidth for audio and video transmission was found to be a critical factor in the quality of telementoring process. Telementoring is safe and feasible. It allows community surgeons with no formal advanced laparoscopic training to benefit from expert intraoperative advice during the performance of advanced laparoscopic procedures. It may also reduce health-care costs by avoiding the need to refer and transfer patients to tertiary care centers.
Rapid Increase in Serum Levels of Matrix Metalloproteinase-9 (MMP-9) Postoperatively is Associated With a Decrease in the Amount of Intracellular MMP-9
Authors: Belizon Avraham , Kirman Irena , Karten Moshe , Jain Suvinit , Whelan Richard L.
Published: March 2006

We have previously demonstrated a significant decrease in the serum concentration of intact insulin-like growth factor-binding protein (IGFBP-3) after laparotomy. IGFBP-3, a major IGF binding protein, inhibits the growth of tumor cells via several mechanisms. Our goal was to determine, in a murine model, whether matrix metalloproteinase-9 (MMP-9), a known protease of IGFBP-3, is responsible for the postoperative decrease in serum IGFBP-3 levels. Six IGFBP-3 transgenic mice on a CD-1 background were used in this study. These mice over-express human IGFBP-3. Sham laparotomy, in the form of a midline abdominal incision, was the test procedure. General anesthesia was established using ketamine and xylazine immediately before a 30-minute sham laparotomy and before preoperative blood sampling, done via retro-orbital venipuncture, 48 hours before surgery. The animals were sacrificed and blood was drawn 24 hours postoperatively. Plasma MMP-9 activity was measured using zymography at each time point (48 hours before and 24 hours after operation). MMP-9 activity was also measured in mononuclear cell lysates at both time points. Zymography analysis demonstrated significantly higher plasma levels of MMP-9 postoperatively compared with preoperative levels (81 RU vs 40 RU; P < .05). In contrast, mononuclear cell levels of MMP-9 were significantly higher preoperatively compared with postoperative levels (37.5 RU vs. 0.75 RU, P < .05). Plasma levels of MMP-9, a known protease of IGFBP-3, are significantly elevated postoperatively. In addition, mononuclear cells that store MMP-9 are depleted of it postoperatively. This suggests that rapid MMP-9 release by mononuclear cells leads to an increase in serum levels of this protease postoperatively. Further studies will elucidate mechanisms of MMP-9–related IGFBP-3 depletion.
Computing Support for Information-Rich Laparoscopy
Authors: Seales W. Brent , Clarke Duncan
Published: March 2006

Developments in the architecture and organization of high-performance general-purpose computer systems are largely ignored by the technology infrastructure of the modern laparoscopic surgical suite. The current state of technology for laparoscopy is a camera and monitor linked via a controller that distributes analog or digital video signals without regard to their content. This article discusses the opportunities that will be created by inserting general-purpose high-performance computing into the information stream between camera and display. We envision that the use of this technology will radically transform laparoscopy from its current state as “surgery by pictures” into an entirely new, information-rich surgical environment.
A Marketing-Oriented Perspective on Physician Selection
Authors: Kelley Scott W. , Schwartz Richard W.
Published: March 2006

The process of selecting a physician is an inherently difficult one for patients. Physician selection is often made from limited information, and in many cases, the information used as the basis for physician selection is obtained indirectly through either medical service providers or other consumers or patients. When selecting a physician, patients tend to rely on personal sources of information and place importance on the reputational aspects of the health-care provider, organization, and experience. Patient expectations for the technical aspects of the health-care experience are stringent and must be met or exceeded by physicians and other health-care providers to compete long-term in the health-care market place. Beyond this, health-care providers can favorably influence patient perceptions of the health-care experience by excelling at the functional aspects of service provision (ie, the interpersonal-and process-oriented attributes). This article examines the physician selection process and provides marketing-oriented recommendations for addressing some of the challenges patients encounter when selecting a physician.
Health Care as a Fixed-Cost Industry: Implications for Delivery
Authors: Taheri Paul A. , Butz David A.
Published: March 2006

Most health-care costs are fixed and sunk. Fixed costs do not vary with the level of patient activity, and once sunk they cannot be easily reversed. We must rethink how we manage the expensive investments in our health care infrastructure, which is where most costs lie. The conventional approaches to rationing care have failed. Physicians have been told to lower the cost of care by rationing resources. This rationing includes reducing the length of patients’ hospital stays but this does not work as intended. A new paradigm advocates making more and better use of existing assets and by pursuing improvements incrementally and at the bedside. Elements include flexing intensive care unit beds, improving operating room efficiencies, and rationalizing health care capacity.
Pouch Perineal Rectosigmoidectomy: A Case Report
Authors: Baig Mirza K. , Galliano Domingo , Larach Jorge A. , Weiss Eric G. , Wexner Steven D. , Nogueras Juan J.
Published: March 2006

Many surgical methods have been described for the treatment of full-thickness rectal prolapse. Rarely, unusually large lengths of colon must be excised, thus resulting in a significant loss of the absorptive function of the remaining colon. We present an unusual case in which an extraordinary length of the colon was excised and a perineal reservoir was created in the form of a colonic J-pouch to improve continence.
Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells
Authors: Lee Jun Ho , Kim Young Mi , Kim Nam Wook , Kim Jie Wan , Her Erk , Kim Bo Kyung , Kim Jong Hyun , Ryu Sung Ho , Park Jong Woo , Seo Dong Wan , Han Jeung Whan , Beaven Michael A. , Choi Wahn Soo
Published: March 2006

Mast cells are responsible for IgE-mediated allergic reactions. Phospholipase D1 (PLD1) and PLD2 regulate mast cell activation, but the mechanisms remain unclear. Here we show that PLD2 associates with and promotes activation of Syk, a key enzyme in mast cell activation. Antigen stimulation resulted in increased association and colocalization of Syk with PLD2 on the plasma membrane as indicated by coimmunoprecipitation and confocal microscopy. This association was dependent on tyrosine phosphorylation of Syk but not on PLD2 activity. In vitro, PLD2 interacted via its Phox homology (PX) domain with recombinant Syk to induce phosphorylation and activation of Syk. Furthermore, overexpression of PLD2 or catalytically inactive PLD2K758R enhanced antigen-induced phosphorylations of Syk and its downstream targets, the adaptor proteins LAT and SLP-76, while expression of a PLD2 siRNA blocked these phosphorylations. Apparently, the interaction of PLD2 with Syk is an early critical event in the activation of mast cells.
Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency
Authors: Borghans José A. , Bredius Robbert G. , Hazenberg Mette D. , Roelofs Helene , Jol-van der Zijde Els C. , Heidt Jeroen , Otto Sigrid A. , Kuijpers Taco W. , Fibbe Willem E. , Vossen Jaak M. , Miedema Frank , van Tol Maarten J.
Published: March 2006

The immune system of patients with severe combined immunodeficiency (SCID) reconstitutes to a large extent during the first years after hematopoietic stem cell transplantation (HSCT). It was suggested, however, that accelerated loss of thymus output may cause impaired immune function at the long term. To address this issue, we studied patients with SCID who underwent allogeneic HSCT 5 to 32 years earlier and identified early determinants of long-term T-cell reconstitution. A variety of immune parameters were analyzed both early (1-4 years) and late (5-32 years) after HSCT. Late after HSCT, a clear distinction could be made between a group of 8 patients with impaired T-cell reconstitution and 11 patients with good immune reconstitution. Importantly, in patients with decreased long-term T-cell reconstitution, T-cell recovery was already poor early after HSCT, demonstrating that long-term immune failure was not caused by accelerated loss of thymus output or long-term graft failure, but resulted from poor early grafting. The number of T-cell receptor excision circles (TRECs) early after HSCT was most predictive for long-term T-cell reconstitution. Frequent monitoring of T-cell immunity and TREC numbers early after HSCT may thus serve to timely identify patients who will fail to reconstitute properly and who may need additional treatment.
Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin
Authors: Khan Zia A. , Melero-Martin Juan M. , Wu Xiao , Paruchuri Sailaja , Boscolo Elisa , Mulliken John B. , Bischoff Joyce
Published: March 2006

Infantile hemangiomas are composed of endothelial cells (ECs), endothelial progenitor cells (EPCs), as well as perivascular and hematopoietic cells. Our hypothesis is that hemangioma-derived EPCs (HemEPCs) differentiate into the mature ECs that comprise the major compartment of the tumor. To test this, we isolated EPCs (CD133+/Ulex europeus– I+) and mature ECs (CD133–/Ulex europeus–I+) from proliferating hemangiomas and used a previously described property of hemangioma-derived ECs (HemECs), enhanced migratory activity in response to the angiogenesis inhibitor endostatin, to determine if HemEPCs share this abnormal behavior. Umbilical cord blood–derived EPCs (cbEPCs) were analyzed in parallel as a normal control. Our results show that HemEPCs, HemECs, and cbEPCs exhibit increased adhesion, migration, and proliferation in response to endostatin. This angiogenic response to endostatin was consistently expressed by HemEPCs over several weeks in culture, whereas HemECs and cbEPCs shifted toward the mature endothelial response to endostatin. Similar mRNA-expression patterns among HemEPCs, HemECs, and cbEPCs, revealed by microarray analyses, provided further indication of an EPC phenotype. This is the first demonstration that human EPCs, isolated from blood or from a proliferating hemangioma, are stimulated by an angiogenesis inhibitor. These findings suggest that EPCs respond differently from mature ECs when exposed to angiogenic or antiangiogenic signals.
Differential regulation by leukotrienes and calcium of Fcγ receptor-induced phagocytosis and Syk activation in dendritic cells versus macrophages
Authors: Canetti Claudio , Aronoff David M , Choe Mun , Flamand Nicolas , Wettlaufer Scott , Toews Galen B , Chen Gwo-Hsiao , Peters-Golden Marc
Published: March 2006

Macrophage (MØ) phagocytosis via the Fc receptor for immunoglobulin G (FcγR) requires the spleen tyrosine kinase (Syk) and serves an important antimicrobial function. We have reported previously that FcγR-mediated ingestion and Syk activation in MØ are amplified by and depend on the proinflammatory lipid mediator leukotriene B4 (LTB4). Although FcγR-mediated ingestion is also important for antigen uptake, there is no information about LTB4 regulation of these processes in dendritic cells (DCs). In this study, we compared murine bone marrow (BM)-derived DCs to MØ from BM, peritoneum, and the pulmonary alveolar space. Neither phagocytosis nor Syk activation in DCs was influenced by exogenous LTB4. Unlike the various MØ populations, Syk activation in DCs was likewise unaffected by pharmacologic or genetic strategies to inhibit endogenous LTB4 synthesis or to block the high-affinity LTB4 receptor BLT1. DCs were refractory to regulation by LTB4 despite the fact that they expressed BLT1 and mobilized intracellular calcium in response to its ligation. This resistance to LTB4 in DCs instead reflected the fact that in contrast to MØ, Syk activation in DCs was itself entirely independent of calcium. These results identify a fundamental difference in FcγR signaling between DCs and MØ, which may relate to the divergent, functional consequences of target ingestion in the two cell types.
CD8 T cells expressing killer Ig-like receptors and NKG2A are present in cord blood and express a more naïve phenotype than their counterparts in adult blood
Authors: Warren Hilary S , Rana Purna M , Rieger Duncan T , Hewitt Kimberly A , Dahlstrom Jane E , Kent Alison L
Published: March 2006

We report that natural killer receptors (NKR) for major histocompatibility complex (MHC) class I molecules (MHC-NKR), the inhibitory killer immunoglobulin-like receptors (KIR), and the CD94/NKG2A receptor are present on a small proportion of CD8 T cells in cord blood. On average, 1.67% of CD8 T cells in cord blood express KIR, and 0.74% expresses NKG2A, approximately fivefold less than in adult blood. CD8 T cells expressing MHC-NKR were present at similar levels in cord blood from preterm and term infants, and it is important that their presence was independent of placental pathology or infection. Cord blood CD8 T cells expressing MHC-NKR were relatively homogeneous and entirely CD27+, mostly CC chemokine receptor 7− and granzyme B−, with a majority being CD45RA+ and with no evidence for a skewed distribution of T cell receptor-Vβ when tested in KIR+ cells. This contrasted with adult blood, which was more heterogeneous, and where a majority of CD8 T cells expressing MHC-NKR was CD27− and granzyme B+. Functional studies revealed that cord blood KIR+ CD8 T cells were as capable as KIR− CD8 T cells in their ability to proliferate in response to CD3 ligation, yet it is interesting that they were more capable than KIR− CD8 T cells in their ability to secrete interferon-γ. These data suggest that cord blood CD8 T cells expressing MHC-NKR are a unique subset of cells, distinct from those in adult blood, and may represent a less-differentiated population.
Adenoviral-encoded antigens are presented efficiently by a subset of dendritic cells expressing high levels of αvβ3 integrins
Authors: Harui Airi , Roth Michael D , Vira Darshni , Sanghvi Mihir , Mizuguchi Hiroyuki , Basak Saroj K
Published: March 2006

Dendritic cells (DC) play a central role in antigen presentation and are often targeted by adenoviral (Ad)-based gene therapy. However, DC lack the coxsackie-Ad receptor, and little is known about the process by which they acquire and present Ad-encoded antigens. We examined the expression of ανβ3 integrins (CD51/CD61) on mouse bone marrow-derived DC (BM-DC) and their susceptibility to transduction by Ad vectors. Less than 10% of BM-DC precursors expressed CD51, but expression increased over time in culture with granulocyte macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. After 7 days, 28 ± 1.7% of CD11c+ DC expressed high levels of CD51 (CD51hi), and the remaining DC expressed low levels of CD51 (CD51lo). CD51hi CD express higher major histocompatibility complex type 1 (MHC I); however, both of the DC subsets expressed similar levels of MHC II and costimulatory molecules. When exposed to a first-generation Ad vector, transgene expression was restricted to the CD51hi DC subset and blocked by soluble peptides expressing an arginine, glycine, aspartic acid (RGD) sequence, confirming the role of integrins in viral entry. Consistent with this, a modified Ad expressing an RGD-binding sequence in its fiber knob (Ad-RGD) transduced the CD51hi DC subset with significantly higher efficiency. When BM-DC were transduced with an Ad-expressing ovalbumin (Ad-OVA), the CD51hi subset proved superior in activating OT-I (T cell receptor-OVA) T cells. Similar to in vitro effects, systemic administration of GM-CSF/IL-4 increased the expression of CD51 on splenic DC and rendered these cells susceptible to Ad transduction. These results suggest that a limited subset of DC expressing high levels of ανβ3 integrins is preferentially transduced by Ad vectors and activates CD8+ T cell responses against Ad-encoded antigens.
Psychotherapy plus antidepressant for panic disorder with or without agoraphobia
Authors: Furukawa Toshi A. , Watanabe Norio , Churchill Rachel
Published: April 2006

Background

Panic disorder can be treated with psychotherapy, pharmacotherapy or a combination of both.

Aims

To summarise the evidence concerning the short- and long-term benefits and adverse effects of a combination of psychotherapy and antidepressant treatment.

Method

Meta-analyses and meta-regressions were undertaken using data from all relevant randomised controlled trials identified by a comprehensive literature search. The primary outcome was relative risk (RR) of response.

Results

We identified 23 randomised comparisons (21 trials involving a total of 1709 patients). In the acute-phase treatment, the combined therapy was superior to antidepressant pharmacotherapy (RR=1.24, 95% CI 1.02–1.52) or psychotherapy (RR=1.16, 95%CI 1.03–1.30). After termination of the acute-phase treatment, the combined therapy was more effective than pharmacotherapy alone (RR=1.61, 95% CI 1.23–2.11) and was as effective as psychotherapy (RR=0.96, 95% CI 0.79–1.16).

Conclusions

Either combined therapy or psychotherapy alone may be chosen as first-line treatment for panic disorder with or without agoraphobia, depending on the patient's preferences.
Cost-utility of brief psychological treatment for depression and anxiety
Authors: Hakkaart-Van Roijen Leona , Van Straten Annemieke , Al Maiwenn , Rutten Frans , Donker Marianne
Published: March 2006

Background

The cost-utility of brief therapy compared with cognitive–behavioural therapy (CBT) and care as usual in the treatment of depression and anxiety has not yet been determined.

Aims

To assess the cost-utility of brief therapy compared with CBT and care as usual.

Method

A pragmatic randomised controlled trial involving 702 patients was conducted at 7 Dutch mental healthcare centres (MHCs). Patients were interviewed at baseline and then every 3 months over a period of 1.5 years, during which time data were collected on direct costs, indirect costs and quality of life.

Results

The mean direct costs of treatment at the MHCs were significantly lower for brief therapy than for CBT and care as usual. However, after factoring in other healthcare costs and indirect costs, no significant differences between the treatment groups could be detected. We found no significant differences in quality-adjusted life-years between the groups.

Conclusions

Cost-utility did not differ significantly between the three treatment groups.
Ethnic differences among patients in high-security psychiatric hospitals in England
Authors: Leese Morven , Thornicroft Graham , Shaw Jenny , Thomas Stuart , Mohan Rajesh , Harty Mari Anne , Dolan Mairead
Published: April 2006

Background

Black (Black Caribbean and Black African) patients are over-represented in admissions to general adult and medium-security psychiatric services in England.

Aims

To describe the socio-demographic, clinical and offence characteristics of patients in high-security psychiatric hospitals (HSPHs) in England, and to compare admission rates and unmet needs by ethnic group.

Method

A total of 1255 in-patients were interviewed, and their legal status, socio-demographic characteristics and individual treatment needs were assessed.

Results

Black patients in HSPHs are over-represented by 8.2 times (range 3.2–24.4, 95% CI 7.1–9.3), are more often male (P=0.037), and are more often diagnosed with a mental illness and less often diagnosed with a personality disorder or learning disability (P< 0.001) than White patients. Unmet needs were significantly less common among White than among Black patients (mean values of 2.22v.2.62, difference=0.40, 95% CI 0.06–0.73).

Conclusions

Compared with the proportion of Black patients in the general population in their region of origin, a much higher proportion of Black patients were admitted to HSPHs, and fewer of their needs were met.
Has the referral of older adults with dementia changed since the availability of acetylcholinesterase inhibitors and the NICE guidelines?
Authors: O'Loughlin Christopher , Darley Jon
Published: March 2006

Aims and Method

To investigate whether patients with dementia are referred to specialist services earlier in the disease since the launch of acetylcholinesterase inhibitors and the publication of the National Institute for Clinical Excellence (NICE) guidelines for the use of these drugs. All referrals to old age psychiatry services in two 6-month periods in 1996 and 2003 were surveyed retrospectively for diagnosis, Mini-Mental State Examination (MMSE) score and use of acetylcholinesterase inhibitors.

Results

The mean MMSE score at referral increased from 18.8 to 21.5 (P=0.0005) between 1996 and 2003. Acetylcholinesterase inhibitors were prescribed for 35% of all patients and 58% of patients that would be suitable according to NICE guidelines in the 2003 group.

Clinical Implications

The earlier referral of patients with dementia to mental health services is encouraging.
Drug services in England and Wales: a survey of treatment providers and their medical leads
Authors: Airey Nick , McLaren Stuart
Published: April 2006

Aims and Method

We undertook a postal questionnaire survey of drug action teams in England and Wales with the aim of clarifying the nature of statutory specialist drug services.

Results

Of 159 drug action teams, 110 (69%) responded; 64 (58%) reported that mental health trusts exclusively provided their specialist drug services. Other providers were primary care and acute trusts, the non-statutory sector and social services. The majority of medical leads were psychiatrists (123 senior posts with 20% vacant/occupied by a locum), then general practitioners (GPs) (42) and other specialists (4).

Clinical Implications

Specialist drug services are offered by a range of treatment providers, with the medical lead being taken by GPs and other specialists in some areas. In view of the current difficulty in recruiting psychiatrists, we propose that alternative training pathways are considered for addiction specialists.
Service innovations: a dedicated drug treatment service for dementia
Authors: Sheehan Bart , Saad Karim
Published: April 2006

Aims and Method

To describe a targeted domiciliary drug treatment service for dementia and to establish clinical outcomes for its patients. All new referrals in a 6-month period were included. Data on clinical and demographic background, service performance and cognitive, functional and behavioural outcomes were recorded.

Results

Of 96 patients initiated on antidementia drugs, most had dementia of mild to moderate severity, and had heterogenous diagnoses. Significant improvements in cognition, behaviour and function were found.

Clinical Implications

A dedicated domiciliary drug treatment service for dementia achieved high levels of clinical activity and outcomes at least as good as clinical trials. This service model may be an attractive choice.
Development of an Emergency Department Work Score to Predict Ambulance Diversion
Authors: Epstein Stephen K. , Tian Lu
Published: March 2006

Objectives:
The authors sought to develop and validate an emergency department (ED) work score that could be used in real time to quantify crowding and staff workload in an ED. This work score could be used by public health officials to direct ambulance traffic based on an objective measure of ED status and to track ED conditions over time. In addition, the authors sought to determine which portion of ED care was most responsible for crowding.

Methods:
The setting was a tertiary teaching hospital with an emergency medicine residency. A number of ED parameters were measured throughout 2003 and then matched to times that an ED was on diversion status. Odd months of the year were used to develop the standard and even months to validate the standard. A marginal logistic regression analysis was used to develop the standard. The decision to divert ambulances was used as the criterion for ED crowding.

Results:
The logistic regression demonstrated excellent correlation between the work score and diversion status. At the point of maximum inflection of the receiver operating characteristic curve, the work score predicted diversion status with 86% sensitivity and 80% specificity.

Conclusions: An ED work score was successfully developed and internally validated. External validation should be performed before widespread use.
Association of High-Level MRP1 Expression With Poor Clinical Outcome in a Large Prospective Study of Primary Neuroblastoma
Authors: Haber Michelle , Smith Janice , Bordow Sharon B. , Flemming Claudia , Cohn Susan L. , London Wendy B. , Marshall Glenn M. , Norris Murray D.
Published: March 2006

Purpose

We have previously shown in a retrospective study that expression of the multidrug transporter gene MRP1 (ABCC1) is associated with outcome in neuroblastoma. We have now undertaken a prospective analysis to examine the independent prognostic significance of MRP1 expression in a large cohort of primary untreated neuroblastomas.

Patients and Methods

Two hundred nine diagnostic neuroblastoma samples from patients prospectively enrolled onto the Pediatric Oncology Group biology protocol 9047 were analyzed for expression of the MRP1, MDR1, MYCN, and TRKA genes using real-time polymerase chain reaction. Expression levels were correlated with established prognostic indicators and disease outcome.

Results

MRP1 expression was detected in all tumors analyzed, and levels were significantly higher in tumors with versus without MYCN amplification (P < .0001). High levels of MRP1 were highly predictive of both event-free survival (EFS; P < .001) and overall survival (OS; P < .001). High-level MYCN and low-level TRKA were also predictive of poor outcome. MDR1 expression demonstrated no prognostic significance. After adjustment for the effect of statistically significant prognostic indicators in multivariate models, MRP1 expression retained significant prognostic value for both EFS (hazard ratio = 3.0; P = .0011) and OS (hazard ratio = 2.5; P = .0095), whereas MYCN amplification did not have prognostic significance.

Conclusion

The results of this prospective study confirm our earlier findings and support a clinically relevant role for MRP1 gene expression in neuroblastoma. These findings have implications for the biology, prognosis, and treatment of this disease and provide evidence that MRP1 is a bone fide molecular target for reversing chemotherapy resistance in aggressive drug-refractory neuroblastoma.
Phase I Clinical Evaluation of Weekly Administration of the Novel Vascular-Targeting Agent, ZD6126, in Patients With Solid Tumors
Authors: Beerepoot Laurens V. , Radema Sandra A. , Witteveen Els O. , Thomas Tawnie , Wheeler Catherine , Kempin Sanford , Voest Emile E.
Published: March 2006

Purpose

ZD6126 is a novel vascular-targeting agent that induces selective effects on the morphology of endothelial cells by disrupting the tubulin cytoskeleton. This leads to cell detachment and tumor vessel congestion, resulting in extensive central necrosis in a range of tumor xenograft models. Results from a phase I dose-escalation study of ZD6126 are reported.

Patients and Methods

Thirty-two patients with advanced cancer received weekly ZD6126 infusion (5 to 28 mg/m2). Assessments for safety and pharmacokinetics were performed. Circulating endothelial cells (CECs) were quantified as a pharmacodynamic marker of vascular damage.

Results

Maximum concentrations of the active species were observed 5 to 25 minutes from the start of infusion, and decayed in a biexponential manner with a half-life of 1 to 3 hours. Maximum serum concentration and area under the time-concentration curve increased with dose in a linear fashion across the dose range of 5 to 28 mg/m2. One patient treated at 10 mg/m2 with a history of ischemic heart disease experienced acute myocardial infarction 2 weeks after drug discontinuation. Four others had asymptomatic creatine phosphokinase–muscle-brain elevation. Maximum-tolerated dose (MTD) was reached at 20 mg/m2/wk. Dose-limiting toxicities at 28 mg/m2 were hypoxia caused by pulmonary embolism and an asymptomatic decrease in left ventricular ejection fraction. No objective antitumor responses were observed. CEC levels increased in the hours after infusion, indicating potential effect of the compound on the vasculature.

Conclusion

ZD6126 administered as a weekly infusion was clinically well tolerated. The MTD was reached at 20 mg/m2.
Predictive Factors for Outcome in a Phase II Study of Gefitinib in Second-Line Treatment of Advanced Esophageal Cancer Patients
Authors: Janmaat Maarten L. , Gallegos-Ruiz Mariëlle I. , Rodriguez José A. , Meijer Gerrit A. , Vervenne Walter L. , Richel Dick J. , Van Groeningen Cees , Giaccone Giuseppe
Published: March 2006

Purpose

The efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib was assessed in a phase II study in patients with advanced esophageal cancer. Several biologic features were investigated as potential markers of gefitinib activity.

Patients and Methods

Patients with advanced esophageal cancer, who had failed one line of prior chemotherapy, were administered gefitinib 500 mg/d. Response was evaluated every 8 weeks. Tumor material obtained before gefitinib treatment was investigated for gene mutations in EGFR, k-ras, and PIK3CA; protein expression levels of EGFR, p-Akt, and p-Erk; and EGFR gene amplification.

Results

Of the 36 enrolled patients, one (2.8%) achieved a partial response, 10 (27.8%) had stable disease, 17 (47.2%) experienced progression on treatment, and eight (22.2%) were not assessable for response. The progression-free survival time was 59 days, and the median overall survival time was 164 days. Although EGFR or PIK3CA mutations were absent, k-ras mutations were found in two patients with progressive disease. High EGFR gene copy number was identified in two patients experiencing partial response or progressive disease. A higher disease control rate (response plus stable disease) was observed in females (P = .038) and in patients with squamous cell carcinoma (SCC; P = .013) or high EGFR expression (P = .002).

Conclusion

Gefitinib has a modest activity in second-line treatment of advanced esophageal cancer. However, the patient outcome was significantly better in female patients and in patients demonstrating high EGFR expression or SCC histology. The selection of esophageal cancer patients for future studies with EGFR-TKIs based on the level of EGFR expression in their tumors or SCC histology should be considered.
Tumor Thymidylate Synthase 1494del6 Genotype As a Prognostic Factor in Colorectal Cancer Patients Receiving Fluorouracil-Based Adjuvant Treatment
Authors: Dotor Emma , Cuatrecases Miriam , Martínez-Iniesta María , Navarro Matilde , Vilardell Felip , Guinó Elisabeth , Pareja Laura , Figueras Agnés , Molleví David G. , Serrano Teresa , de Oca Javier , Peinado Miguel A. , Moreno Víctor , Germà Josep Ramón , Capellá Gabriel , Villanueva Alberto
Published: March 2006

Purpose

The purpose of this study was to analyze the value of germline and tumor thymidylate synthase (TS) genotyping as a prognostic marker in a series of colorectal cancer patients receiving adjuvant fluorouracil (FU) -based treatment.

Patients and Methods

One hundred twenty-nine colorectal cancer patients homogeneously treated with FU plus levamisole or leucovorin in the adjuvant setting were included. TS enhancer region, 3R G > C single nucleotide polymorphism (SNP), and TS 1494del6 polymorphisms were assessed in both fresh-frozen normal mucosa and tumor. Mutational analyses of TS and allelic imbalances were studied in all primary tumors and in 18 additional metachronic metastases. TS protein immunostaining was assessed in an expanded series of 214 tumors. Multivariate Cox models were adjusted for stage, differentiation, and location.

Results

Tumor genotyping (frequency of allelic loss, 26%) showed that the 3R/3R genotype was associated with a better outcome (hazard ratio [HR] = 0.38; 95% CI, 0.16 to 0.93; P = .020 for the recessive model). 3R G > C SNP genotyping did not add prognostic information. Tumor TS 1494del6 allele (frequency of allelic loss, 36%) was protective (for each allele with the deletion, based on an additive model, HR = 0.42; 95% CI, 0.22 to 0.82; P = .0034). Both polymorphisms were in strong linkage disequilibrium (D' = 0.71, P < .001), and the 3R/–6 base pair (bp) haplotype showed a significant overall survival benefit compared with the most prevalent haplotype 2R/+6bp (HR = 0.42; 95% CI, 0.20 to 0.85; P = .017). No TS point mutation was detected in primary tumors or metastases. TS protein immunostaining was not associated with survival or any of the genotypes analyzed.

Conclusion

Tumor TS 1494del6 genotype may be a prognostic factor in FU-based adjuvant treatment of colorectal cancer patients.
High WT1 Expression After Induction Therapy Predicts High Risk of Relapse and Death in Pediatric Acute Myeloid Leukemia
Authors: Lapillonne Hélène , Renneville Aline , Auvrignon Anne , Flamant Cyril , Blaise Annick , Perot Christine , Lai Jean-Luc , Ballerini Paola , Mazingue Françoise , Fasola Sylvie , Dehée Axelle , Bellman Françoise , Adam Mircéa , Labopin Myriam , Douay Luc , Leverger Guy , Preudhomme Claude , Landman-Parker Judith
Published: March 2006

Purpose

To determine whether minimal residual disease (MRD) measured by Wilms' tumor gene 1 (WT1) expression is a prognostic marker in pediatric acute myeloid leukemia (AML), we quantified WT1 transcript by real-time quantitative-polymerase chain reaction in 92 AML at diagnosis and during follow-up.

Patients and Methods

Patients (median age, 6 years; cytogenetics, favorable 27%, intermediate 59%, poor 13%) were treated between 1995 and 2002 and enrolled in Leucémie aiguë Myéloblastique Enfant (LAME) 89/91, LAME 99 pilot study and Acute Promyelocytic Leukemia French collaborative protocols. With a median follow-up of 26 months, event-free survival was 56% with a standard deviation (SD) of 5% and overall survival of 62.5% with an SD of 6%. WT1 copy number was normalized by TATA box binding protein gene transcripts and expressed as WT1/TBP × 1,000 ratio. Median WT1 ratio in normal patient controls was 12 (range, 0 to 57). A level over two SD than normal bone marrow controls (ie, WT1 ratio > 50), was considered as significant overexpression.

Results

At diagnosis, WT1 overexpression was detected in 78% of patients (72 of 92 patients; median copy ratio, 2231). The WT1 values were significantly higher (P = .01) in favorable cytogenetics and lower (P < .0001) in M5-FAB subtype, 11q23 rearrangements (P < .001), and infants (P = .003) and demonstrate a strong correlation with fusion transcript AML1-ETO, PML-RARα expression. After induction treatment, WT1 ratio was analyzed in 46 of 72 patients and found above 50 in nine of 36 patients and five of 25 patients at D35-50 and 3 to 5 months, respectively. WT1 ratio > 50 after induction is an independent prognostic risk factor of relapse (P = .002) and death (P = .02).

Conclusion

WT1 quantification is an informative molecular marker for MRD in pediatric AML and is now performed as prospective analysis in ELAM02 protocol.