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1.
Behav Brain Res ; 437: 114148, 2023 02 02.
Article in English | MEDLINE | ID: mdl-36206822

ABSTRACT

BACKGROUND: Using balanced placebo designs, seminal alcohol administration research has shown individuals' beliefs about whether they have consumed alcohol, irrespective of the actual presence of alcohol, can determine level of alcohol consumption and impact social behavior. Despite the known effect of expecting alcohol on drinking behavior, few studies have used the placebo manipulation to directly investigate the neural underpinnings of the expectancy-related effects that occur following perceived alcohol consumption in humans. The present paper examined placebo responses in the laboratory to better understand the neural basis for the psychological phenomenon of expectancies. METHODS: As part of a larger within-subjects study design, healthy young adults (N = 22, agemean+SD=23 +1) completed resting state fMRI scans and measures of subjective response before and after consuming placebo beverages. Effect of placebo beverage consumption (pre- versus post-beverage consumption) on functional connectivity within prefrontal cortical networks was examined using the CONN Toolbox. Relations between perceived subjective response to alcohol with functional connectivity response following placebo beverage consumption were examined. RESULTS: Compared to pre-beverage scan, placebo beverage consumption was associated with increased positive functional connectivity between right nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex (pFDR<0.05). Subjective ratings of intoxication (i.e., feeling 'drunk') positively correlated with placebo beverage-related increases in nucleus accumbens - subcallosal cingulate cortex functional connectivity. CONCLUSION: Results suggest placebo response to alcohol is associated with increased functional connectivity within a key reward network (nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex) and put forth a mechanism by which alcohol expectancies may contribute to the subjective experience of intoxication.


Subject(s)
Ethanol , Nucleus Accumbens , Humans , Young Adult , Nucleus Accumbens/diagnostic imaging , Ethanol/pharmacology , Alcohol Drinking , Prefrontal Cortex , Magnetic Resonance Imaging , Neural Pathways/diagnostic imaging
2.
Tomography ; 6(1): 23-33, 2020 03.
Article in English | MEDLINE | ID: mdl-32280747

ABSTRACT

Small-animal imaging is an essential tool that provides noninvasive, longitudinal insight into novel cancer therapies. However, considerable variability in image analysis techniques can lead to inconsistent results. We have developed quantitative imaging for application in the preclinical arm of a coclinical trial by using a genetically engineered mouse model of soft tissue sarcoma. Magnetic resonance imaging (MRI) images were acquired 1 day before and 1 week after radiation therapy. After the second MRI, the primary tumor was surgically removed by amputating the tumor-bearing hind limb, and mice were followed for up to 6 months. An automatic analysis pipeline was used for multicontrast MRI data using a convolutional neural network for tumor segmentation followed by radiomics analysis. We then calculated radiomics features for the tumor, the peritumoral area, and the 2 combined. The first radiomics analysis focused on features most indicative of radiation therapy effects; the second radiomics analysis looked for features that might predict primary tumor recurrence. The segmentation results indicated that Dice scores were similar when using multicontrast versus single T2-weighted data (0.863 vs 0.861). One week post RT, larger tumor volumes were measured, and radiomics analysis showed greater heterogeneity. In the tumor and peritumoral area, radiomics features were predictive of primary tumor recurrence (AUC: 0.79). We have created an image processing pipeline for high-throughput, reduced-bias segmentation of multiparametric tumor MRI data and radiomics analysis, to better our understanding of preclinical imaging and the insights it provides when studying new cancer therapies.


Subject(s)
Deep Learning , Magnetic Resonance Imaging/methods , Sarcoma/diagnostic imaging , Soft Tissue Neoplasms/diagnostic imaging , Animals , Mice , Neoplasm Recurrence, Local
3.
PLoS One ; 14(4): e0207555, 2019.
Article in English | MEDLINE | ID: mdl-30958825

ABSTRACT

In designing co-clinical cancer studies, preclinical imaging brings unique challenges that emphasize the gap between man and mouse. Our group is developing quantitative imaging methods for the preclinical arm of a co-clinical trial studying immunotherapy and radiotherapy in a soft tissue sarcoma model. In line with treatment for patients enrolled in the clinical trial SU2C-SARC032, primary mouse sarcomas are imaged with multi-contrast micro-MRI (T1 weighted, T2 weighted, and T1 with contrast) before and after immune checkpoint inhibition and pre-operative radiation therapy. Similar to the patients, after surgery the mice will be screened for lung metastases with micro-CT using respiratory gating. A systems evaluation was undertaken to establish a quantitative baseline for both the MR and micro-CT systems against which others systems might be compared. We have constructed imaging protocols which provide clinically-relevant resolution and contrast in a genetically engineered mouse model of sarcoma. We have employed tools in 3D Slicer for semi-automated segmentation of both MR and micro-CT images to measure tumor volumes efficiently and reliably in a large number of animals. Assessment of tumor burden in the resulting images was precise, repeatable, and reproducible. Furthermore, we have implemented a publicly accessible platform for sharing imaging data collected during the study, as well as protocols, supporting information, and data analyses. In doing so, we aim to improve the clinical relevance of small animal imaging and begin establishing standards for preclinical imaging of tumors from the perspective of a co-clinical trial.


Subject(s)
Lung Neoplasms/diagnostic imaging , Multimodal Imaging , Sarcoma/diagnostic imaging , Tumor Burden , X-Ray Microtomography , Animals , Humans , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Mice , Neoplasm Metastasis , Sarcoma/pathology
4.
Oncogene ; 35(14): 1868-75, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-26234681

ABSTRACT

Approximately 30% of patients with soft-tissue sarcoma die from pulmonary metastases. The mechanisms that drive sarcoma metastasis are not well understood. Recently, we identified miR-182 as a driver of sarcoma metastasis in a primary mouse model of soft-tissue sarcoma. We also observed elevated miR-182 in a subset of primary human sarcomas that metastasized to the lungs. Here, we show that myogenic differentiation factors regulate miR-182 levels to contribute to metastasis in mouse models. We find that MyoD directly binds the miR-182 promoter to increase miR-182 expression. Furthermore, mechanistic studies revealed that Pax7 can promote sarcoma metastasis in vivo through MyoD-dependent regulation of pro-metastatic miR-182. Taken together, these results suggest that sarcoma metastasis can be partially controlled through Pax7/MyoD-dependent activation of miR-182 and provide insight into the role that myogenic transcription factors have in sarcoma progression.


Subject(s)
MicroRNAs/genetics , MyoD Protein/genetics , PAX7 Transcription Factor/genetics , Sarcoma/genetics , Animals , Cell Differentiation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Mice , MicroRNAs/metabolism , Muscle Development/genetics , MyoD Protein/metabolism , PAX7 Transcription Factor/metabolism , Promoter Regions, Genetic , Sarcoma/pathology
5.
PLoS One ; 10(12): e0143208, 2015.
Article in English | MEDLINE | ID: mdl-26636762

ABSTRACT

BACKGROUND: Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. METHODS: The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). RESULTS: The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). CONCLUSION: Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.


Subject(s)
Cranial Irradiation/methods , Hippocampus/radiation effects , Animals , DNA/radiation effects , Dose Fractionation, Radiation , Hippocampus/physiopathology , Radiotherapy, Intensity-Modulated , Rats , Rats, Wistar , Treatment Outcome
6.
Phys Med Biol ; 58(21): 7791-801, 2013 Nov 07.
Article in English | MEDLINE | ID: mdl-24140983

ABSTRACT

There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose-volume relationships with tumour control and normal tissue damage. For these studies it is vital that image guidance systems and target positioning are accurately aligned (IGRT), in order to deliver dose precisely and accurately according to the treatment plan. In this work we investigate the IGRT targeting accuracy of the X-RAD 225 Cx system from Precision X-Ray using high-resolution 3D dosimetry techniques. Small cylindrical PRESAGE® dosimeters were used with optical-CT readout (DMOS) to verify the accuracy of 2.5, 1.0, and 5.0 mm X-RAD cone attachments. The dosimeters were equipped with four target points, visible on both CBCT and optical-CT, at which a 7-field coplanar treatment plan was delivered with the respective cone. Targeting accuracy (distance to agreement between the target point and delivery isocenter) and cone alignment (isocenter precision under gantry rotation) were measured using the optical-CT images. Optical-CT readout of the first 2.5 mm cone dosimeter revealed a significant targeting error of 2.1 ± 0.6 mm and a cone misalignment of 1.3 ± 0.1 mm. After the IGRT hardware and software had been recalibrated, these errors were reduced to 0.5 ± 0.1 and 0.18 ± 0.04 mm respectively, within the manufacturer specified 0.5 mm. Results from the 1.0 mm cone were 0.5 ± 0.3 mm targeting accuracy and 0.4 ± 0.1 mm cone misalignment, within the 0.5 mm specification. The results from the 5.0 mm cone were 1.0 ± 0.2 mm targeting accuracy and 0.18 ± 0.06 mm cone misalignment, outside of accuracy specifications. Quality assurance of small field IGRT targeting and delivery accuracy is a challenging task. The use of a 3D dosimetry technique, where targets are visible on both CBCT and optical-CT, enabled identification and quantification of a targeting error in 3D. After correction, the targeting accuracy of the irradiator was verified to be within 0.5 mm (or 1.0 mm for the 5.0 mm cone) and the cone alignment was verified to be within 0.2 mm (or 0.4 mm for the 1.0 mm cone). The PRESAGE®/DMOS system proved valuable for end-to-end verification of small field IGRT capabilities.


Subject(s)
Radiotherapy, Image-Guided/instrumentation , Cone-Beam Computed Tomography , Feasibility Studies , Radiometry
7.
J Phys Conf Ser ; 444: 12070, 2013.
Article in English | MEDLINE | ID: mdl-24454521

ABSTRACT

There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose-volume relationships with tumor control and normal tissue damage. In this work we investigate the IGRT targeting accuracy of the XRad225Cx system from Precision x-Ray using high resolution 3D dosimetry techniques. Initial results revealed a significant targeting error of about 2.4mm. This error was reduced to within 0.5mm after the IGRT hardware and software had been recalibrated. The facility for 3D dosimetry was essential to gain a comprehensive understanding of the targeting error in 3D.

8.
Med Phys ; 39(6Part14): 3766, 2012 Jun.
Article in English | MEDLINE | ID: mdl-28517298

ABSTRACT

PURPOSE: To verify the accuracy of TG-61 based dosimetry with MOSFET technology using a tissue-equivalent mouse phantom. METHODS: Accuracy of mouse dose between a TG-61 based look-up table was verified with MOSFET technology. The look-up table followed a TG-61 based commissioning and used a solid water block and radiochromic film. A tissue-equivalent mouse phantom (2 cm diameter, 8 cm length) was used for the MOSFET method. Detectors were placed in the phantom at the head and center of the body. MOSFETs were calibrated in air with an ion chamber and f-factor was applied to derive the dose to tissue. In CBCT mode, the phantom was positioned such that the system isocenter coincided with the center of the MOSFET with the active volume perpendicular to the beam. The absorbed dose was measured three times for seven different collimators, respectively. The exposure parameters were 225 kVp, 13 mA, and an exposure time of 20 s. RESULTS: For a 10 mm, 15 mm, and 20 mm circular collimator, the dose measured by the phantom was 4.3%, 2.7%, and 6% lower than TG-61 based measurements, respectively. For a 10 × 10 mm, 20 × 20 mm, and 40 × 40 mm collimator, the dose difference was 4.7%, 7.7%, and 2.9%, respectively. CONCLUSIONS: The MOSFET data was systematically lower than the commissioning data. The dose difference is due to the increased scatter radiation in the solid water block versus the dimension of the mouse phantom leading to an overestimation of the actual dose in the solid water block. The MOSFET method with the use of a tissue- equivalent mouse phantom provides less labor intensive geometry-specific dosimetry and accuracy with better dose tolerances of up to ± 2.7%.

9.
Proc SPIE Int Soc Opt Eng ; 7622: 76223G.1-76223G.9, 2010 Feb 15.
Article in English | MEDLINE | ID: mdl-21243034

ABSTRACT

Gating in small animal imaging can compensate for artifacts due to physiological motion. This paper presents a strategy for sampling and image reconstruction in the rodent lung using micro-CT. The approach involves rapid sampling of free-breathing mice without any additional hardware to detect respiratory motion. The projection images are analyzed post-acquisition to derive a respiratory signal, which is used to provide weighting factors for each projection that favor a selected phase of the respiration (e.g. end-inspiration or end-expiration) for the reconstruction. Since the sampling cycle and the respiratory cycle are uncorrelated, the sets of projections corresponding to any of the selected respiratory phases do not have a regular angular distribution. This drastically affects the image quality of reconstructions based on simple filtered backprojection. To address this problem, we use an iterative reconstruction algorithm that combines the Simultaneous Algebraic Reconstruction Technique with Total Variation minimization (SART-TV). At each SART-TV iteration, backprojection is performed with a set of weighting factors that favor the desired respiratory phase. To reduce reconstruction time, the algorithm is implemented on a graphics processing unit. The performance of the proposed approach was investigated in simulations and in vivo scans of mice with primary lung cancers imaged with our in-house developed dual tube/detector micro-CT system. We note that if the ECG signal is acquired during sampling, the same approach could be used for phase-selective cardiac imaging.

11.
Article in English | MEDLINE | ID: mdl-16869760

ABSTRACT

Lung cancer is a devastating disease that presents a challenge to basic research to provide new steps toward therapeutic advances. The cell-type-specific responses to oncogenic mutations that initiate and regulate lung cancer remain poorly defined. A better understanding of the relevant signaling pathways and mechanisms that control therapeutic outcome could also provide new insight. Improved conditional mouse models are now available as tools to improve the understanding of the cellular and molecular origins of adenocarcinoma. These models have already proven their utility in proof-of-principle experiments with new technologies including genomics and imaging. Integrated thinking to apply technological advances while using the appropriate mouse model is likely to facilitate discoveries that will significantly improve lung cancer detection and intervention.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Disease Models, Animal , ErbB Receptors/genetics , Genes, p53 , Genes, ras , Genomics , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Mice , Mice, Mutant Strains , Mutation , Neoplastic Stem Cells/pathology , Signal Transduction , ras Proteins/metabolism
12.
Clin Exp Rheumatol ; 21(5): 647-9, 2003.
Article in English | MEDLINE | ID: mdl-14611118

ABSTRACT

Cardiac conduction disease is an infrequent complication of Wegener's granulomatosis (WG). We describe a case demonstrating an association between WG and complete atrioventricular dissociation. This manifestation was initially interpreted as Lyme disease based on these cardiac findings, arthritis, myalgias and positive Lyme serology. The clinical overlap between these disorders and the appropriate use of respective serologies is discussed.


Subject(s)
Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/diagnosis , Heart Block/etiology , Lyme Disease/diagnosis , Adult , Female , Humans
13.
Thorac Cardiovasc Surg ; 51(2): 62-6, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12730812

ABSTRACT

OBJECTIVE: Segmental varicose degeneration of the autogenous greater saphenous vein may limit its use in infrainguinal bypass surgery. Wrapping a PTFE prosthesis around dilated veins has emerged as an option to create externally reinforced vein bypasses. Results regarding graft patency and limb salvage were analyzed. METHODS: Between September 1995 and January 2001, 35 infrainguinal bypass operations in 33 patients were performed with greater saphenous veins exhibiting segmental varicose dilatation. Grafts were followed by duplex scan and retrospective analysis of graft patency and limb salvage was performed. RESULTS: One bypass prompted successful revision for early occlusion. Four bypasses required additional reintervention during follow-up. 48 months primary, primary assisted and secondary patency rates were 66%, 82% and 82%, respectively, with a limb salvage rate of 97%. Duplex scan failed to demonstrate stenosis of the reinforced vein segments or aneurysmal degeneration of the residual vein. CONCLUSION: External reinforcement with a PTFE prosthesis allows the use of autogenous greater saphenous veins with varicose dilatation and enables the construction of all autogenous bypasses with promising graft patency and limb salvage.


Subject(s)
Blood Vessel Prosthesis Implantation/instrumentation , Inguinal Canal/surgery , Polytetrafluoroethylene/therapeutic use , Varicose Veins/therapy , Aged , Aged, 80 and over , Coated Materials, Biocompatible/therapeutic use , Combined Modality Therapy , Female , Follow-Up Studies , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/mortality , Humans , Male , Middle Aged , Popliteal Vein/diagnostic imaging , Popliteal Vein/physiopathology , Popliteal Vein/surgery , Radiography , Reoperation , Retrospective Studies , Saphenous Vein/diagnostic imaging , Saphenous Vein/physiopathology , Saphenous Vein/surgery , Severity of Illness Index , Survival Analysis , Time , Time Factors , Treatment Outcome , Varicose Veins/mortality , Varicose Veins/physiopathology , Vascular Patency/physiology
14.
Surg Endosc ; 16(1): 54-6, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11961605

ABSTRACT

BACKGROUND: Laparoscopic esophagogastric fundoplication is an effective treatment for severe gastroesophageal reflux disease (GERD), although its role in the very young is still largely undetermined. We review our surgical outcome in infants with severe GERD, comparing laparoscopic (LNF) with open (ONF) Nissen fundoplication. METHODS: This study reviewed 55 consecutive Nissen fundoplications performed for GERD on infants less than 1 year old at our institution between January 1996 and June 2000. The follow-up period for LNF averaged 14.2 months (range, 3.3-42 months), as compared with 16.5 months (range, 1-37.1 months) for ONF (p was not significant, t-test). Surgical outcome was compared in terms of the following parameters: average operative time, times to initiation and completion of feeding schedule, postoperative complications, and recurrence rates. RESULTS: For the study, 53 infants were divided into two groups: LNF (n = 39; 73.6%) and ONF (n = 14; 26.4%). The average operating time for LNF was 120 +/- 24 min (range, 60-195 min), as compared with 91 +/- 21 min (range, 60-135 min) for ONF (p < 0.05, t-test). Time to initiation of postoperative feeding schedule was 1.3 +/- 0.3 days for LNF, as compared with 3 +/- 0.9 days for ONF (p < 0.05, t-test). Full feedings were reached in 1.7 +/- 0.6 days for LNF, as compared with 1.3 +/- 0.9 for ONF (p was not significant, t-test). During the short-term follow-up period, recurrent reflux developed in 2/14 ONF patients (14.3%) as compared with 1/39 LNF patients (2.6%) (p < 0.05). CONCLUSIONS: We conclude that in addition to sparing infants the morbidity of celiotomy, laparoscopic Nissen fundoplication had a surgical outcome comparable to that of traditional open fundoplication in infants with severe GERD. Importantly, resumption of goal nutritional regimens was equally efficient in both groups.


Subject(s)
Fundoplication/methods , Laparoscopy/methods , Child, Preschool , Humans , Infant , Video-Assisted Surgery/methods
15.
Zentralbl Chir ; 126(11): 897-900, 2001 Nov.
Article in German | MEDLINE | ID: mdl-11753800

ABSTRACT

UNLABELLED: Hereditary pancreatitis is an autosomal dominant disease. Recently, the genetic defect has been mapped to chromosome 7q35 and consists mainly of a point mutation in exon 3 of the cationic trypsinogen gene which causes an Arg(CGC)-His(CAC) substitution at residue 117. In patients with hereditary pancreatitis the estimated cumulative risk for pancreatic carcinoma to age 70 approaches 40 %. Thus, the role of hereditary pancreatitis in the pathogenesis of pancreatic carcinoma is of interest. PATIENTS AND METHODS: DNA was extracted from peripheral blood (n = 16), fresh tumor tissue (n = 29) and formalin fixed and paraffin embedded tumor tissue (n = 5) of 50 patients with ductal adenocarcinoma of the pancreas. We specifically amplified exon 3 and the intronic flanking sequences of the cationic trypsinogen gene by nested PCR and performed restriction fragment length polymorphism analysis using the restriction enzyme Afl III. In patients with hereditary pancreatitis the G : A point mutation creates a recognition site for Afl III which is not present in unaffected individuals. RESULTS: None of the 50 patients with ductal adenocarcinoma of the pancreas revealed the G : A point mutation in exon 3 of the cationic trypsinogen gene which is characteristic of hereditary pancreatitis. In addition sequencing of exon 3 did not reveal any other mutations in the DNA of patients with pancreatic adenocarcinoma. CONCLUSION: Although hereditary pancreatitis markedly increases the risk for pancreatic cancer, it is rare and probably of little significance with respect to the pathogenesis of the majority of pancreatic adenocarcinomas.


Subject(s)
Adenocarcinoma/etiology , Pancreatic Neoplasms/etiology , Pancreatitis/complications , Pancreatitis/genetics , Adolescent , Aged , Child , Child, Preschool , DNA/analysis , DNA Primers , DNA, Neoplasm/analysis , Exons/genetics , Humans , Infant , Nucleic Acid Amplification Techniques , Point Mutation , Polymerase Chain Reaction , Risk Factors , Trypsinogen/genetics
16.
Zentralbl Chir ; 126(5): 357-63, 2001 May.
Article in German | MEDLINE | ID: mdl-11396243

ABSTRACT

Primary anastomosis is becoming increasingly favoured because of the shorter hospital stay even in emergency operations on the colon and rectum. This appears entirely justified when an objective of cost-effective medicine has been set. At our hospital between September 1985 and February 1999, 365 patients were operated on because of diverticular disease. The data from 346 of these patients were evaluated. 202 of these cases were elective; 144 were carried out on an emergency or urgent basis. In 223 cases, a primary anastomosis (Stage I and II according to Hinchey) and in 56 patients a double-barreled colostomy with a distal mucus fistula were performed. 57 patients had a too short rectum-sigma stump and were operated in two stages, according to Hartmann. Of 223 patients with a primary anastomosis, 6 (2.7%) developed an insufficiency of the anastomosis, whereby 3 (1.3%) of these patients subsequently died. Of the patients with Hartmann operation, 11 (19.3%) died due to the sequelae of peritonitis and only 2 patients died following insufficiency of the Hartmann's stump. Of the patients with a mucus fistula, 10 patients (17.9%) died as a result of complications of peritonitis. Of the 113 patients (21 died) with a discontinuity resection, 66 (71%) had their colostomy closed. There were no cases of anastomosis insufficiency and no patient died as a result of the colostomy closure. In the interest of the patients in septic diverticulitis the safest surgical procedure, the discontinuity resection, should be chosen.


Subject(s)
Anastomosis, Surgical , Colostomy , Diverticulitis, Colonic/surgery , Peritonitis/surgery , Postoperative Complications/mortality , Adult , Aged , Aged, 80 and over , Cause of Death , Diverticulitis, Colonic/mortality , Female , Follow-Up Studies , Germany , Humans , Male , Middle Aged , Peritonitis/mortality , Reoperation , Surgical Wound Dehiscence/mortality , Surgical Wound Dehiscence/surgery , Survival Rate
17.
Nature ; 409(6817): 131, 2001 Jan 11.
Article in English | MEDLINE | ID: mdl-11196617
18.
Vasa ; 29(3): 173-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11037714

ABSTRACT

BACKGROUND: Conflicting theories on the development of primary varicosis have led to the molecular biological investigation of the vein wall or, more accurately, of the extracellular matrix. It was the aim of this study to quantify matrix expression and to compare pathological changes in the vein wall with valve-orientated staging of varicosis, in order to determine indicators of the primary cause of varicosis. MATERIALS AND METHODS: Three hundred seventy-two tissue specimens of greater saphenous veins were obtained from 17 patients with varicosities and categorised according to Hach stage and procurement site. The specimens were compared with 36 specimens collected from six patients without varicosities, incubated with fluorescence-stained antibodies for collagen 4, laminin, fibronectin and tenascin prior to being assessed with confocal laser scan microscopy. In addition, 22 vein specimens (16 varicose, 6 normal veins) serving as negative controls were investigated. RESULTS: Image analysis and statistical evaluation showed that compared with normal veins, varicose veins are associated with a significant increase in matrix protein expression for collagen 4, laminin and tenascin. A trend towards an increase in matrix expression was further observed for fibronectin. There was, however, no difference between varicose veins and clinically healthy vein segments inferior to a varicose segment. CONCLUSION: If the findings of the present investigation can be confirmed by other studies, alterations in the vein wall may be regarded as the primary cause of varicosis and valvular insufficiency as the result of these changes.


Subject(s)
Extracellular Matrix/pathology , Varicose Veins/pathology , Extracellular Matrix Proteins/analysis , Humans , Microscopy, Confocal , Microscopy, Fluorescence , Saphenous Vein/pathology , Venous Insufficiency/pathology
19.
Psychiatr Clin North Am ; 23(2): 403-13, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10909116

ABSTRACT

One of the characteristics of the best outpatient treaters is their capacity to manage their own anxieties so as not to interfere with their patients' progress. This does not mean "sitting on," shutting out, or otherwise ignoring those signals to prevent their intruding into the therapeutic space. On the contrary, this requires that a clinician be acutely aware of his or her internal dialogue and be able to listen to use it to facilitate the treatment. This has meant simultaneously listening to oneself while paying complete attention to one's patient. This paradox is part of the nature of this work and remains one of its important features. Today, those who choose to treat psychiatric patients in this setting are presented with many more such paradoxes, including the necessity of being aware of (1) populations needing to be served while providing the best care for individual patients; (2) limited resources; and (3) balancing ethical, fiscal, legal, and clinical concerns. This article demonstrates that the successful development of outpatient services in a managed care environment requires attention to these same tensions on a larger scale. It also shows that understanding the evolution of managed care and the myriad competing interests involved are necessary to be able to care successfully for psychiatric patients.


Subject(s)
Ambulatory Care , Managed Care Programs , Mental Health Services , Case Management , Humans , United States
20.
Am Surg ; 66(6): 569-72; discussion 573, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10888133

ABSTRACT

Children with stage II empyema often fail traditional medical management, frequently succumbing to the effective albeit morbid clutches of thoracotomy. Video-assisted thoracoscopic surgery (VATS) has been recently introduced as a viable and potentially less morbid alternative to open thoracotomy. We review our VATS experience in children with empyema, assessing surgical outcome. Between August 1996 and March 1999, 13 patients at our institution with stage II empyema that did not respond to conventional medical management underwent a modified VATS with decortication. Data from retrospective chart review reflects intraoperative findings and postoperative course, including average time to defervescence, removal of thoracostomy tube, and hospital discharge. VATS was completed in all 13 patients. All intraoperative cultures of pleural fluid and fibrinopurulent debris obtained at VATS showed no growth. The average time to defervescence was 2.2 days (range, 0-4 days) and to removal of thoracostomy tube 3.6 days (range, 2-5 days). Average total chest tube days in patients with pre-VATS thoracostomy (n = 6) was 14.5 days (range, 8-37 days) versus 3.1 days (range, 2-5 days) in patients (n = 7) who underwent primary VATS (t test, p < 0.05). The average time to surgical discharge after VATS was 5.8 days (range, 3 to 19 days). All patients were well on follow-up clinic visits without delayed complications. VATS can be performed safely and effectively in children with stage II empyema, thus avoiding the morbidity of open thoracotomy and decortication. Importantly, early application of VATS significantly relieves patients of unnecessary days of thoracostomy drainage.


Subject(s)
Empyema, Pleural/surgery , Thoracic Surgery, Video-Assisted , Adolescent , Child , Child, Preschool , Empyema, Pleural/classification , Humans , Infant , Infant, Newborn , Retrospective Studies , Thoracic Surgery, Video-Assisted/methods
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