Stenosis of the celiac trunk is associated with anastomotic leak after Ivor-Lewis esophagectomy.

Transthoracic esophagectomy with gastric tube formation is the surgical treatment of choice for esophageal cancer. The surgical reconstruction induces changes of gastric microcirculation, which are recognized as potential risk factors of anastomotic leak. This prospective observational study investigates the association of celiac trunk (TC) stenosis with postoperative anastomotic leak. One hundred fifty-four consecutive patients with esophageal cancer scheduled for Ivor-Lewis esophagectomy were included. Preoperative staging computed tomography (CT) was used to identify TC stenosis. Any narrowing of the lumen due to atherosclerotic changes was classified as stenosis. Percentage of stenotic changes was calculated using the North American Symptomatic Carotid Endarterectomy Trial formula. Multivariable analysis was used to identify possible risk factors for leak. The overall incidence of TC stenosis was 40.9%. Anastomotic leak was identified in 15 patients (9.7%). Incidence of anastomotic leak in patients with stenosis was 19.4% compared to 2.3% in patients without stenosis. Incidence of stenosis in patients with leak was 86.7% (13 of 15 patients) and significantly higher than 38.8% (54 of 139 patients) in patients without leak (P < 0.001). There was a significant difference in median degree of TC stenosis (50.0% vs 39.4%; P = 0.032) in patients with and without leak. In the multivariable model, TC stenosis was an independent risk factor for anastomotic leak (odds ratio: 5.98, 95% CI: 1.58-22.61). TC stenosis is associated with postoperative anastomotic leak after Ivor-Lewis esophagectomy. Routine assessment of TC for possible stenosis is recommended to identify patients at risk.

Supplementation with nutrients modulating insulin-like growth factor-1 negatively correlated with changes in the levels of pro-inflammatory cytokines in community-dwelling elderly people at risk of undernutrition.

BACKGROUND: Suboptimal nutrition accompanied by chronic low-grade increases in circulating cytokine levels is more common in elderly people. We explored the improvement in nutritional status, especially in the level of insulin-like growth factor-1 (IGF-1) and its relationship with changes in circulating cytokine levels, after providing extra protein and energy content to community-dwelling older adults at risk of undernutrition. METHODS: Sixty nondiabetic subjects, aged ≥65 years and living independently in a community for elderly people, with a serum pre-albumin level ≤30 mg dL-1 and a body mass index <25 kg m-2 , were recruited. The subjects were followed for a 2-week pre-intervention period, during which they maintained routine dietary habits. This was followed by an intervention period, during which they received oral nutritional supplementation for 2 weeks. RESULTS: Following 2 weeks of intervention, there were significant increases in total lymphocyte count (TLC) and insulin-like growth factor (IGF)-1, pre-albumin and transferrin compared to baseline. Body weight and mid-arm circumference significantly increased without alteration of tricep skinfold thickness at the end of the intervention. There was a significant reduction in interleukin (IL)-6 levels and a trend toward a decrease in the tumor necrosis factor (TNF)-α levels. At baseline, age was negatively correlated with IGF-1 levels and positively correlated with IL-6 and TNF-α levels. The change (▵, from baseline) in IGF-1 level was positively correlated with age and negatively correlated with ▵IL-6 and ▵TNF-α. CONCLUSIONS: A 2-week intervention with oral nutritional supplementation improved nutritional status and decreased circulating cytokine levels. Specifically, ▵IGF-1 was negatively correlated with changes in pro-inflammatory cytokine levels in community-dwelling elderly people at risk of undernutrition. (Clinicaltrials.gov: NCT02656186).

Effects of early contrast-enhanced computed tomography on clinical course and complications in patients with acute pancreatitis.

PURPOSE: To investigate the effect of an early contrast-enhanced computed tomography (CECT) on clinical course and complications of acute pancreatitis (AP). MATERIAL AND METHODS: 58 patients with AP who had at least one CECT examination were analyzed retrospectively. Laboratory as well as clinical data, and results from the assessment of disease severity (CT severity index (CTSI) and its modified (MCTSI) version) were analyzed. The primary endpoint was the development of severe complications, defined as death, respiratory failure, acute renal failure, and the need for invasive interventions. Patients were divided into two groups: an early group (CECT within the first 48 h after the onset of symptoms, n = 32) and a late group (CECT > 48 h after the onset of symptoms, n = 26). Multivariate regression analysis was performed to identify risk factors for severe complications. RESULTS: There were no statistically significant differences between both groups concerning baseline characteristics, CTSI, and MCTSI. Complications occurred more often in the early CECT group (p = 0.008). Multivariate logistic regression analysis identified an early CECT and a severe MCTSI as independent risk factors for the occurrence of severe complications (p = 0.02 and p = 0.002, respectively). CONCLUSION: CECT performed within the first 48 h after the onset of symptoms is associated with an unfavorable outcome in AP.

Clinic efficacy and safety of ultrasound-guided Mammotome-assisted surgery for patients with breast benign tumors.

OBJECTIVE: The aim of this study was to assess the efficacy of ultrasound-guided Mammotome-assisted resection vs. conventional open surgery for benign breast tumors. PATIENTS AND METHODS: From July 2019 to December 2020, 134 suitable patients with benign breast cancers treated at our institution (Breast Surgery Department) were recruited and randomly allocated (1:1) to receive either Mammotome-assisted tumor excision (observation group) or open surgery (control group). The primary endpoint was clinical effectiveness, with surgical outcomes, complications, and satisfaction as secondary endpoints. RESULTS: Mammotome-assisted surgery resulted in shorter operative time, scar length, and postoperative healing time and less intraoperative bleeding volume vs. open surgery (p<0.001). Mammotome-assisted surgery was associated with a significantly higher clinical efficacy vs. open surgery (p<0.05). Patients receiving Mammotome-assisted surgery had a lower incidence of complications vs. those given open surgery (p<0.05). A significantly higher satisfaction was observed in patients given Mammotome-assisted surgery vs. open surgery (p<0.05). CONCLUSIONS: In comparison to standard open surgery, ultrasound-guided Mammotome-assisted surgery provides a viable alternative for breast benign tumor removal with superior efficacy, shorter operating time, less trauma, higher safety, fewer complications, and higher patient satisfaction.

[Thrombotic occlusion of the extracorporeal circulation during hepatic chemosaturation despite targeted anticoagulation : A case report]. / Thrombotischer Verschluss der extrakorporalen Zirkulation während hepatischer Chemosaturation trotz zielgerechter Antikoagulation : Ein Fallbericht.

Percutaneous hepatic chemosaturation is a treatment option for unresectable primary or secondary liver tumors. In this procedure the part of the inferior vena cava (VCI) that collects blood from the hepatic veins is isolated using a double balloon catheter. Like this, systemic distribution of the chemotherapeutic agent melphalan which is administered via the hepatic artery can be prevented. After passage through the liver and drainage from the retrohepatic VCI, the chemosaturated blood passes through two extracorporeal filters. Subsequently, the filtered blood is returned via the jugular vein. The procedure is often accompanied by severe hemodynamic instability, the cause of which is still not completely understood. In addition, coagulation management of extracorporeal circulation is often challenging. The authors report a case in which a thrombus formed in the returning leg of the extracorporeal circulation despite sufficient activated clotting time (ACT). Targeted problem search and resolution were necessary simultaneously to hemodynamic stabilization and interdisciplinary collaboration to successfully perform the intervention and provide the patient with safe treatment.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

How COVID-19 kick-started online learning in medical education-The DigiMed study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts. We aimed to evaluate students' attitudes to online learning to provide a broad scientific basis to guide future development of medical education. METHODS: Overall, 3286 medical students from 12 different countries participated in this cross-sectional, web-based study investigating various aspects of online learning in medical education. On a 7-point Likert scale, participants rated the online learning situation during the pandemic at their medical schools, technical and social aspects, and the current and future role of online learning in medical education. RESULTS: The majority of medical schools managed the rapid switch to online learning (78%) and most students were satisfied with the quantity (67%) and quality (62%) of the courses. Online learning provided greater flexibility (84%) and led to unchanged or even higher attendance of courses (70%). Possible downsides included motivational problems (42%), insufficient possibilities for interaction with fellow students (67%) and thus the risk of social isolation (64%). The vast majority felt comfortable using the software solutions (80%). Most were convinced that medical education lags behind current capabilities regarding online learning (78%) and estimated the proportion of online learning before the pandemic at only 14%. In order to improve the current curriculum, they wish for a more balanced ratio with at least 40% of online teaching compared to on-site teaching. CONCLUSION: This study demonstrates the positive attitude of medical students towards online learning. Furthermore, it reveals a considerable discrepancy between what students demand and what the curriculum offers. Thus, the COVID-19 pandemic might be the long-awaited catalyst for a new "online era" in medical education.

Comparative analysis of CGUARD embolic prevention stent with Casper-RX and Wallstent for the treatment of carotid artery stenosis.

Stent protected Angioplasty of extracranial carotid artery stenosis using the dual-layered CGUARD stent is a novel treatment option. In this study we evaluate the feasibility and the safety of the CGUARD in symptomatic and asymptomatic patients in comparison to Casper-RX and Wallstent. This is a multi-center study of consecutive patients treated with the CGUARD, Casper-RX and Wallstent at two German high volume neurovascular centers between April 2017 and May 2018. Patient characteristics, neuroimaging data and angiographic outcome were retrospectively analyzed. The primary end points of the study were acute occlusion of the carotid stent and symptomatic intracerebral hemorrhage (sICH). Carotid artery stenting was performed in 76 patients; of those 26 (34%) were treated with the CGUARD, 25 (33%) with Casper-RX, and 25 (33%) with Wallstent. In 58/76 (76%) cases carotid artery stenosis was symptomatic with a median baseline National Institutes of Health Stroke Scale of 4. Angioplasty and stenting as part of a mechanical thrombectomy for acute ischemic stroke was performed in 25/76 (33%) patients. Baseline patient characteristics were similar between the treatment groups, except for a higher portion of scheduled cases in the Casper-RX group. There were no significant differences in the rate of acute in stent occlusions (CGUARD, 2/26 (8%); Casper-RX, 1/25(4%); Wallstent, 1/25 (4%)) and postinterventional sICH (1/26 (4%), 0/25(0%), 0/25 (0%)). Clinical outcome at discharge did not differ between groups. Treatment of carotid artery stenosis using CGUARD is feasible with a good safety profile comparable to that of Casper-RX and Wallstent.

[Thoracic and abdominal imaging in immunocompromised patients]. / Radiologische Diagnostik von Thorax und Abdomen bei immunkompromittierten Patienten.

The number of patients with immunosuppression is rising worldwide. The spectrum of diseases and pathogens in these patients differs widely from that of immunocompetent patients due to frequent opportunistic infections. Symptoms are sometimes unspecific, and imaging plays a key role in the management of these patients. The lungs are a frequent site of infection in immunosuppressed patients. Chest X­ray is the starting point for radiological diagnostics, but shows only limited sensitivity and specificity for infections with atypical pathogens. Thus, computed tomography (CT) is of great importance and allows a better distinction between viral, bacterial, or fungal infections, as well as other noninfectious diseases. Even with CT, however, is exact specification of the pathogen unfortunately not possible. CT is also the main diagnostic tool for assessment of the abdomen, particularly in patients presenting with acute abdomen or when sonographic findings are inconclusive. Moreover, CT allows diagnostic and therapeutic interventions such as percutaneous biopsies, or abscess and fluid drainage.

An ion optics study for KSTAR neutral beam injector development.

Ion optics of three accelerator geometries was studied in terms of an analytic linear optics analysis, a numerical simulation using the IGUN program, an optical multichannel measurement of Doppler-shifted H(alpha) lines, and a water-flow calorimetry on the beam absorbing target. In general, there was a reasonable agreement observed between the four analysis methods and thus the theoretical analyses can be utilized with confidence for design iteration.

CO2 pneumoperitoneum increases survival in mice with polymicrobial peritonitis.

PURPOSE: Laparoscopic techniques are commonly used in patients with bacterial peritonitis. CO2 is known to suppress local and systemic inflammatory responses. Nonetheless, an active immune system is needed to contain bacterial contamination of the abdominal cavity. Therefore, we investigated the early and late effects of CO2 pneumoperitoneum on the ability of mice to overcome polymicrobial peritonitis. MATERIAL AND METHODS: Male C57/B6 mice were subjected to pneumoperitoneum with CO2 or helium, or underwent a midline laparotomy. In a first set, changes of arterial blood gases were monitored. In further experiments, polymicrobial peritonitis was induced after 1 h of pneumoperitoneum/laparotomy by cecal ligation and puncture. In a second set of experiments polymicrobial peritonitis was induced 4 h prior to exposure to pneumoperitoneum/laparotomy. After the interventions, survival rates (early survival: 6 to 48 h; late survival > 48 h) were monitored for 7 days. RESULTS: There was no significant effect of pneumoperitoneum or laparotomy on arterial blood gas parameters. CO2 pneumoperitoneum significantly reduced the early (6 to 48 h) mortality of subsequent peritonitis after CO2 pneumoperitoneum compared to laparotomy (2/20 vs. 9/25; p < 0.05). The protective effect did not reach significance after 7 days (late mortality). The application of a helium peritoneum did not show any beneficial effect. Application of a CO2 pneumoperitoneum during polymicrobial peritonitis significantly reduced overall mortality (p < 0.05) compared to laparotomy. CONCLUSIONS: The modulation of immune responses by CO2, but not helium pneumoperitoneum, has a significant positive impact on survival during abdominal sepsis in a mouse model. Thus, application of a CO2 pneumoperitoneum may be beneficial in conditions with bacterial contamination of the abdominal cavity.

Exemptions From Mandatory Immunization After Legally Mandated Parental Counseling.

BACKGROUND: The success of health care provider counseling-based interventions to address vaccine hesitancy is not clear. In 2011, Washington State implemented Senate Bill 5005 (SB5005), requiring counseling and a signed form from a licensed health care provider to obtain an exemption. Evaluating the impact of a counseling intervention can provide important insight into population-level interventions that focus on interpersonal communication by a health care provider. METHODS: We used segmented regression and interaction and aggregation indices to assess the impact of SB5005 on immunization coverage and exemption rates in Washington State from school years 1997-1998 through 2013-2014. RESULTS: After SB5005 was implemented, there was a significant relative decrease of 40.2% (95% confidence interval: -43.6% to -36.6%) in exemption rates. This translates to a significant absolute reduction of 2.9 percentage points (95% confidence interval: -4.2% to -1.7%) in exemption rates. There were increases in vaccine coverage for all vaccines required for school entrance, with the exception of the hepatitis B vaccine. The probability that kindergarteners without exemptions would encounter kindergarteners with exemptions (interaction index) decreased, and the probability that kindergarteners with exemptions would encounter other such kindergarteners (aggregation index) also decreased after SB5005. Moreover, SB5005 was associated with a decline in geographic clustering of vaccine exemptors. CONCLUSIONS: States in the United States and jurisdictions in other countries should consider adding parental counseling by health care provider as a requirement for obtaining exemptions to vaccination requirements.

Combined Heart and Kidney Transplantation: A 23-Year Experience.

BACKGROUND: We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. METHODS: From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. RESULTS: The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). CONCLUSIONS: The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Bile duct carcinoma recurrence in the papillary region in a long-term survivor of hilar cholangiocarcinoma: a case report.

BACKGROUND: Because of its high rate of early recurrence and its poor prognosis, long-term survival after cholangiocarcinoma is rare; therefore, only limited information on patients surviving more than 5 years after surgical therapy is available. CASE PRESENTATION: We report the case of a 57-year-old white man who developed a distal bile duct carcinoma 9 years after curative surgical therapy of intrahepatic cholangiocarcinoma. He had undergone a right lobe hemihepatectomy 11 years ago. Nine years later, he was diagnosed with a distal bile duct carcinoma and a duodenopancreatectomy was performed. On histologic examination both carcinomas revealed a tubular and papillary growth pattern with cancer-free resection margins and for both carcinomas there were no signs of lymphatic infiltration or metastatic spreading. Targeted next-generation sequencing showed an identical activating mutation pattern in both carcinomas. CONCLUSIONS: Late recurrence of cholangiocarcinoma, even anatomically distant to the primary, in long-time survivors is possible and could be caused by a distinct tumor biology. A better understanding of the individual tumor biology could help hepatologists as well as hepatobiliary and pancreatic surgeons in their daily treatment of these patients.

Trends in U.S. hospitalizations and inpatient deaths from pneumonia and influenza, 1996-2011.

BACKGROUND: To reduce excess morbidity and mortality of pneumonia and influenza (PI), the Advisory Committee on Immunization Practices has recommended the use of 7-valent pneumococcal conjugate vaccine (PCV7), and incrementally expanded the target group for annual influenza vaccination of healthy persons, to ultimately include all persons ≥6 months of age without contraindications as of the 2010-2011 influenza season. We aimed to capture broader epidemiologic changes by looking at PI collectively. METHODS: Using interrupted time series, we evaluated the changes in the rates of PI hospitalization and inpatient death across three periods defined according to the changes in vaccination policy. We assessed linear trends adjusting for seasonality, sex, and age group, allowing for differential impact across age groups. PI hospitalizations were defined as a principal diagnosis of PI, or a principal diagnosis of sepsis or respiratory failure, accompanied by a secondary diagnosis of PI. RESULTS: Overall annual rates of PI hospitalizations and inpatient deaths declined by 95 per 100,000 (95% CI: 45-145) and by 4.4 per 100,000 (95% CI: 0.9-7.8), respectively. This translates to 295,000 fewer PI hospitalizations and 13,600 fewer PI inpatient deaths than expected based on the average rates from 1996 through 1999. PI hospitalizations dropped the most among seniors aged 65+ by 487 per 100,000, followed by children aged <2, by 228 per 100,000. PI inpatient deaths declined most among seniors aged 65+, by 25.3 per 100,000. CONCLUSIONS: In this nationally representative study, PI hospitalizations and inpatient deaths decreased in U.S. between 1996 and 2011. There is a temporal association with the introduction and widespread use of pneumococcal conjugate vaccines, and the expansion of the target group for annual influenza vaccination to include all persons ≥6 months of age, while it is difficult to attribute these changes directly to specific vaccines used in this era.

Modification to the accelerator of the NBI-1B ion source for improving the injection efficiency.

Minimizing power loss of a neutral beam imposes modification of the accelerator of the ion source for further improvement of the beam optics. The beam optics can be improved by focusing beamlets. The injection efficiencies by the steering of ion beamlets are investigated numerically to find the optimum modification of the accelerator design of the NBI-1B ion source. The beam power loss was reduced by aperture displacement of three edge beamlets arrays considering power loadings on the beamline components. Successful testing and operation of the ion source at 60 keV/84% of injection efficiency led to the possibility of enhancing the system capability to a 2.4 MW power level at 100 keV/1.9 µP.

Radiation Dose Reduction in Computed Tomography-Guided Lung Interventions using an Iterative Reconstruction Technique.

PURPOSE: To compare the radiation doses and image qualities of computed tomography (CT)-guided interventions using a standard-dose CT (SDCT) protocol with filtered back projection and a low-dose CT (LDCT) protocol with both filtered back projection and iterative reconstruction. MATERIALS AND METHODS: Image quality and radiation doses (dose-length product and CT dose index) were retrospectively reviewed for 130 patients who underwent CT-guided lung interventions. SDCT at 120 kVp and automatic mA modulation and LDCT at 100 kVp and a fixed exposure were each performed for 65 patients. Image quality was objectively evaluated as the contrast-to-noise ratio and subjectively by two radiologists for noise impression, sharpness, artifacts and diagnostic acceptability on a four-point scale. RESULTS: The groups did not significantly differ in terms of diagnostic acceptability and complication rate. LDCT yielded a median 68.6% reduction in the radiation dose relative to SDCT. In the LDCT group, iterative reconstruction was superior to filtered back projection in terms of noise reduction and subjective image quality. The groups did not differ in terms of beam hardening artifacts. CONCLUSION: LDCT was feasible for all procedures and yielded a more than two-thirds reduction in radiation exposure while maintaining overall diagnostic acceptability, safety and precision. The iterative reconstruction algorithm is preferable according to the objective and subjective image quality analyses. KEY POINTS: Implementation of a low-dose computed tomography (LDCT) protocol for lung interventions is feasible and safe. LDCT protocols yield a significant reduction (more than 2/3) in radiation exposure. Iterative reconstruction algorithms considerably improve the image quality in LDCT protocols.

The cytokine CSF-1 (M-CSF) expressed by endometrial carcinomas in vivo and in vitro, may also be a circulating tumor marker of neoplastic disease activity in endometrial carcinoma patients.

Endometrial epithelial cell expression of CSF-1 and FMS antigens was studied in vivo and in vitro in 24 human endometrial carcinoma and 11 benign endometrial biopsy specimens. Twenty-one of 24 adenocarcinomas and 4 of 11 benign lesions stained positively (by IHC) with rabbit anti-human CSF-1 antibodies, while all 24 carcinomas and 3 out of 11 benign lesions (all secretory endometrial specimens) showed significant IHC staining (1+ or greater) of epithelial elements and tissue macrophages with a mouse anti-FMS (CSF-1 receptor) monoclonal antibody. CSF-1 levels in plasma from endometrial carcinoma patients (85 samples, 24 patients) were also found to be markedly elevated (some greater than 100 ng/ml) in patients with active or recurrent disease. In vitro, several endometrial carcinoma cell lines were shown to express FMS complementary transcripts and FMS antigen which were very similar if not identical to those expressed in choriocarcinoma cell line positive controls. Autocrine and paracrine effects mediated by tumor or stromally produced CSF-1 and a tumor epithelial cell CSF-1 receptor may therefore contribute to the biological behavior of endometrial neoplasms in vivo and in vitro.

Cardiovascular actions of dopexamine in anaesthetized and conscious dogs.

1. Arterial blood pressure, heart rate and cardiac contractility were measured in pentobarbitone-anaesthetized mongrel dogs and in conscious, instrumented dogs. 2. In anaesthetized dogs (n = 5), dose-response curves were obtained by intravenous infusion of increasing doses of dopexamine (5-20 micrograms kg-1 min-1). Infusions were administered three times to each animal to determine whether the responses were reproducible. Dopexamine increased heart rate and myocardial contractility and decreased blood pressure. The dose-response curves for dopexamine did not differ significantly over time. 3. In a second group of dogs (n = 6), dose-response curves (5-20 mg kg-1 min-1) were obtained as above and repeated after the administration of amitriptyline (2 mg kg-1, i.v.). Amitriptyline caused a non-significant reduction in the inotropic and chronotropic responses to dopexamine. 4. Control dose-response curves for dopexamine (5-50 micrograms kg-1 min-1) were similarly obtained in a third group of dogs (n = 6), and repeated after bilateral vagotomy and sympathetic denervation of the heart. In these animals, a third dose-response curve for dopexamine was obtained after the administration of ICI 118551 (0.2 mg kg-1, followed by 0.2 mg kg-1 h-1). The chronotropic response to dopexamine was significantly reduced after cardiac denervation. There was a small, non-significant reduction in the inotropic and depressor responses after denervation. Administration of ICI 115881 significantly reduced both the inotropic and chronotropic response to dopexamine and caused a non-significant reduction in the depressor response. 5. The effect of raclopride (0.2 mumol kg-1, p.o.) was investigated by comparison of the dose-response curves for dopexamine in a control group of dogs (n = 6) to those obtained in dogs which had been pretreated with raclopride (n = 5). Raclopride had no significant effect on the cardiovascular responses to dopexamine. 6. In conscious, instrumented dogs (n = 5), pretreated with raclopride, dose-related positive inotropic and chronotropic and depressor responses to dopexamine infusions were recorded. The chronotropic responses in conscious animals were significantly greater than those in the anaesthetized animals.7. The results of this study indicate that both the positive inotropic and chronotropic actions of dopamine are due to a combination of direct, Beta2-adrenoceptor-mediated effects and the baroreceptor reflex response to the depressor action of the drug.