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Biomedical subjects

M Heberer

Publications and source records attributed to M Heberer.

At least 19 recordsLinked to original sources
PubMed2000

Identification of genes differentially expressed in melanoma sublines derived from a single surgical specimen characterised by different sensitivity to cytotoxic T-lymphocyte activity.

In this study we used differential display technology in an attempt to obtain an insight into the mechanisms underlying escape of tumour cells to the specific cytotoxic T cell response. A primary tumour cell line and autologous tumour infiltrating lymphocytes were raised from a metastatic melanoma sample (ME15). Upon co-culture of tumour infiltrating lymphocytes with irradiated tumour cells, CTL specific for neoplastic cells were generated and cloned. Using a CTL clone, a cytotoxicity resistant tumour subline (ME15R) was immunoselected. We applied a PCR-based differential display technique to amplify DNA sequences differentially expressed in ME15 sublines sensitive (S) or resistant (R) to specific CTL killing. 10 different sequences whose expression was exclusively detectable in ME15S cells were identified. Five of them matched with known expressed sequence tags encoding products of unidentified function. 2 showed high homology with a mitochondrial mRNA and with the gene encoding the S24 ribosomal protein. Most interestingly, genes coding for glutamine synthetase, TGF-beta-3 and PAX3, a well-characterised transcription factor, were only expressed in ME15S cells. The latter gene was found to be transcribed in all healthy tissues tested, but only in a subgroup of established melanoma cell lines. Taken together, our data underline the relevant potential of differential display technology in the molecular analysis of paired tumour lines endowed with different phenotypic characteristics. Cloning of entire open reading frames and transfection studies are warranted to clarify the role of individual differentially displayed genes in the escape of tumour cells from cellular immune response.

Base Sequence↗
PubMed2000

FLT3 ligand gene expression and protein production in human colorectal cancer cell lines and clinical tumor specimens.

Dendritic cells (DC) are professional antigen presenting cells (APC) whose proliferation and functional differentiation can be induced by hematopoietic growth factors including GM-CSF and FLT3 ligand (FL). Colorectal cancers are known to be infiltrated by dendritic cells (DC) and neoplastic cells have been shown to produce GM-CSF. In this work we investigated FLT3 ligand (FL) gene expression and protein production in human colorectal cancer cell lines and clinical tumor specimens. Using reverse transcription polymerase chain reaction (RT-PCR), 6 out of 6 established tumor lines were found to express to variable extents FL gene. In 1 of them, SW480, FL immunoreactivity could be observed by taking advantage of specific antibodies. In contrast, soluble FL could not be detected in any culture supernatant. FLT3 receptor (FR) gene was not expressed and exogenous addition to the cultures of recombinant FL (rFL) did not affect the proliferation of the tumor lines. FL gene expression was investigated using a densitometry-assisted, semiquantitative RT-PCR in clinical tumor specimens. Specific FL gene transcripts were amplified from 12 of 12 surgical samples. In these cases, FL gene expression of significantly lower intensity was also detected in healthy mucosa sampled in the vicinity (2 cm) or at a distance (10 cm) from neoplastic outgrowth. Immunohistochemical studies identified FL-positive cancer cells in 5 of 5 cases tested. No positivity was detected in healthy mucosa epithelia at a distance from the tumor or in stromal cells. FL content in preoperative sera from colorectal cancer patients (n = 13) did not exceed the levels detected in healthy donors (</= 100 pg/ml).

Colorectal Neoplasms↗
PubMed1999

[Economics in intensive care medicine: rationalization or rationing?].

Four thesis related to economics of intensive care medicine are derived from an analysis of the intensive care unit of the university hospital of Basel, Switzerland, and the respective literature: (1) Intensive care medicine is costly but rationing can be avoided by rationalization. (2) Exemption or withdrawal of intensive care cannot be justified in the absence of accurate predictors of costs and outcomes of individual patients. (3) Intensive care physicians must not act as judges but on behalf of patients incapable of decision making. They must represent patients' interests vis-à-vis authorities and reimbursing institutions. (4) Analyses of cost-efficiency are instrumental for process improvement of intensive care, for negotiations on reimbursement and for the regulatory decisions of the authorities. Tools for economic analyses of intensive care medicine are therefore worthy of further development.

Costs and Cost Analysis↗
PubMed1998

Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules.

In this work, we addressed the possibility to enhance the "in vitro" generation of CTLs recognizing tumor-associated antigens (TAAs) by using an inactivated recombinant vaccinia virus encoding B7.1 and B7.2 costimulatory molecules (rVV-B7.1/2). Antigen presenting cells (APCs) infected by rVV-B7.1/2 and pulsed with MART-1/Melan-A27-35 HLA-A2.1-restricted peptide induced significantly higher specific cytotoxic activity than peptide-loaded APCs infected by wild-type VV, both in VV-sensitized and naive donors. When APCs were infected with a rVV encoding both MART-1/Melan-A27-35 and B7-1/2 (rVV-B7.1/2-M), a significantly more effective CTL generation was observed as compared with cultures stimulated by APCs infected with a rVV encoding the TAA epitope only (rVV-M). These enhancing effects were detectable irrespective of a previous VV-specific sensitization. Most importantly, fibroblasts, devoid of antigen-presenting capacity upon peptide pulsing or infection with rVV-M, could be turned into effective APCs after infection by rVV encoding TAA epitopes and costimulatory molecules. In these experiments, by using separate recombinant viral constructs, we observed a predominant role of B7-1 as compared with B7-2 in the induction of TAA-specific CTLs. Taken together, our data indicate that replication-incompetent rVV encoding TAA epitopes and costimulatory molecules are able to induce highly effective generation of tumor-specific CTLs. Therefore, these vectors could represent valuable clinical tools for immunotherapy of melanoma patients.

Antigen-Presenting Cells↗
PubMed1998

GM-CSF gene expression and protein production in human colorectal cancer cell lines and clinical tumor specimens.

Granulocyte-macrophage colony stimulating factor (GM-CSF) gene expression and protein production were investigated in colorectal cancer cell lines and surgical specimens. In 6 of 6 established tumor lines, expression of the GM-CSF gene was observed by reverse transcription polymerase chain reaction (RT-PCR). Furthermore, for 2 of the lines, the cytokine was detectable in > or = 100 pg/ml amounts in culture supernatants by enzyme-linked immunosorbent assay tests. Addition of recombinant GM-CSF at doses ranging between 30 pg and 30 ng/ml did not appear to affect the proliferation of colorectal cancer cell lines as measured by 3H-thymidine incorporation. GM-CSF gene expression was then examined in surgical specimens by a densitometry-assisted, semiquantitative RT-PCR technique. In the 10 samples analyzed, significantly higher expression was detectable in tumors, as compared with autologous healthy mucosa sampled in the vicinity (2 cm) or at distance (10 cm) from the neoplastic focus. Immunohistochemistry studies performed on 13 specimens led to the identification of intracytoplasmic GM-CSF in tumor cells in 9 samples. In 6 of these, positivity of stromal fibroblasts and lymphocytes adjacent to the tumor was also observed. In contrast, intracellular GM-CSF was only detectable in 2 cases in untransformed epithelial cells, close to the neoplasm, but never in healthy mucosa at distance from the tumor. Infiltration by dendritic cells (DC) was also investigated. In 5 of 8 colorectal cancers tested, DC aggregates accounted for more than 10% of stromal cells. Lower numbers were detectable in healthy mucosa. However, DC infiltration could not be correlated with the presence of GM-CSF-positive neoplastic cells in the tumor specimens. Remarkably, cultured DC were unable to exert significant cytotoxic activity against colorectal cancer cells in vitro.

Aged↗
PubMed1998

C-type lectin-like receptors in peptide-specific HLA class I-restricted cytotoxic T lymphocytes: differential expression and modulation of effector functions in clones sharing identical TCR structure and epitope specificity.

C-type lectin-like inhibitory receptors are heterodimers consisting of CD94 and NKG2-A-B molecules expressed on NK cells and on a subset of activated T lymphocytes. Their inhibitory effects on NK cytotoxicity and on the NK-like activity of T cell clones have been demonstrated, but no data are currently available on antigen-specific class I-restricted cytotoxic T lymphocytes (CTL). We have generated a panel of HLA-A2.1-restricted CTL clones directed against a nonapeptide derived from a melanoma-associated antigen, dopachrome tautomerase (TRP-2). All clones were CD8+ and TCR alphabeta+. About half of them expressed a CD94bright phenotype, whereas the remaining were CD94dim. Only the CD94bright CTL expressed the NKG2-A-B gene, consistent with the expression of a C-type, lectin-like, inhibitory CD94/NKG2-A-B heterodimer. Both CD94bright and CD94dim clones appeared to require similar amounts of synthetic epitope sensitizing target cells. Addition of anti-CD94 mAb resulted in a significant increase of specific killing by CD94bright, but not by CD94dim clones in the presence of suboptimal concentrations of peptide, whereas, when optimal amounts were used, the mAb did not induce a significant modulation of the cytotoxicity. Antigen-induced inward [Ca2+]i fluxes were unaffected, but an enhancement of TCR down-modulation could be observed in the presence of anti-CD94 mAb at high concentration of antigenic peptide. The analysis of the TCR-Vbeta repertoire of the CTL clones by RT-PCR and immunofluorescence revealed that all clones regardless of CD94 phenotype shared Vbeta22 expression. Most importantly, sequence analysis showed that they all expressed identical Vbeta22 TCR rearranged with Jbeta2.1 and Cbeta2. Taken together, these data indicate that different expression of functionally active lectin-like inhibitory receptors can be detected in CTL clones sharing identical TCR sequence and peptide specificity.

Amino Acid Sequence↗
PubMed1998

[Success factors in hospital management].

The hospital environment of most Western countries is currently undergoing dramatic changes. Competition among hospitals is increasing, and economic issues have become decisive factors for the allocation of medical care. Hospitals therefore require management tools to respond to these changes adequately. The balanced scorecard is a method of enabling development and implementation of a business strategy that equally respects the financial requirements, the needs of the customers, process development, and organizational learning. This method was used to derive generally valid success factors for hospital management based on an analysis of an academic hospital in Switzerland. Strategic management, the focus of medical services, customer orientation, and integration of professional groups across the hospital value chain were identified as success factors for hospital management.

Cost-Benefit Analysis↗
PubMed1998

Clinical results using the trochanter stabilizing plate (TSP): the modular extension of the dynamic hip screw (DHS) for internal fixation of selected unstable intertrochanteric fractures.

OBJECTIVE: To evaluate whether the implantation of the modular trochanter stabilizing plate (TSP) in addition to the dynamic hip screw (DHS) prevents excessive telescoping and limb shortening in four-part and selected three-part trochanteric fractures. DESIGN: Prospective clinical study. SETTING: The study was conducted at the trauma unit of the Surgical Department of the University of Basel, Switzerland. PATIENTS: Forty-six consecutive patients with unstable intertrochanteric fractures were treated with an additional TSP super-imposed on the regular DHS at our institution between July 1991 and July 1993. Five patients died before the first follow-up, one patient was lost to follow-up, and another patient refused follow-up. Thus, thirty-nine patients were followed for at least twelve months (mean 14 months, range 12 to 20 months). INTERVENTION: The fractures treated were classified according to the OTA classification, which is based on the AO classification. Seventeen were 31-A2.2, seven were 31-A2.3, and fourteen were 31-A3.3 fractures. RESULTS: Lateralization of the greater trochanter was successfully prevented in all fractures. Limited fracture impaction was found in 90 percent (n = 35) of the patients with telescoping of 9.5 millimeters (range 0 to 30 millimeters), resulting in mean limb shortening of 5.37 millimeters (range 0 to 14.9 millimeters). Four patients suffered limb shortening exceeding fifteen millimeters (range 15.6 to 21.3 millimeters). Functional results were excellent and good in 87 percent of patients and fair in 13 percent according to the Salvati-Wilson score. All fractures had healed six months after the operation. Three complications required a secondary procedure: one from not inserting a second screw parallel to the gliding hip screw to prevent rotation of the head-neck fragment ("antirotation screw"), one because of deep infection, and one because of a refracture after premature implant removal. CONCLUSION: In unstable pertrochanteric fractures with small or missing lateral cortical buttress, the addition of a TSP to the DHS effectively supports the unstable greater trochanter fragment and can prevent rotation of the head-neck fragment. Excessive fracture impaction and consecutive limb shortening was prevented by this additional implant in 90 percent of these patients.

Adult↗
PubMed1997

Nonreplicating recombinant vaccinia virus encoding human B-7 molecules elicits effective costimulation of naive and memory CD4+ T lymphocytes in vitro.

We constructed recombinant vaccinia viruses (recVV) encoding the human T-cell costimulatory molecules B7-1 and B7-2. To abrogate the vaccinia virus transcription termination signal for early genes, the cDNA of B7-1 had to be modified by a T through C sense mutation at position 766. Upon infection with replication incompetent and noncytopathic recVV, several tumor cell lines as well as cultured human fibroblasts expressed the costimulatory molecules. All these cells were capable of providing effective costimulation for proliferation of resting CD4(+) T-cells after infection with recVV encoding B7 molecules. The costimulatory effect could be blocked with CTLA-4 IgG fusion protein, the soluble ligand for B7. RecVV-induced overexpression of B7 on syngeneic EBV-transformed lymphoblastoid B-cells was able to costimulate the proliferative response of CD4(+) memory cells against VV antigens. The possibility of easily engineering a variety of human cells using recVV encoding human B7 molecules holds implications for the future design of vaccination strategies.

B7-1 Antigen↗
PubMed1997

Functional and morphological outcome of knee joint transplantation in dogs depends on control of rejection.

BACKGROUND: The reconstruction of massive osteochondral defects extending to weight-bearing joints remains a surgical challenge. Total knee joint transplantation has been performed experimentally, but these studies lacked prospective evaluation of functional outcome, graft vascularization, and graft viability. METHODS: Replantation and transplantation of vascularized knee joints was performed in dogs (n=4 per group), comparing functional and morphological results during a 6-month follow-up. RESULTS: All replant recipients and three transplant recipients survived the 6-month follow-up period. At this time, duplex sonography and angiography revealed patent anastomoses in all animals. Increases in volumetric flow rates and vascular collateralization were observed in allografts, as compared with replanted joints (100+/-16 ml/min vs. 31+/-15 ml/min at 6 months after transplantation). Bone fusion at the graft-host interface was verified by fluorography in all animals at 3 months after transplantation. Six months after transplantation, microradiographies and computerized tomographies revealed spongialization of the cortical bone and filling of the medullary space by trabecular bone in transplanted joints. Such alterations were not detectable in replanted joints. Chondrocyte viability exceeded 80% in all but one transplanted joint. Lymphocyte infiltration of synovia and arterial walls was detected in all transplanted joints, suggesting the presence of chronic rejection. Weight-bearing capacity recovered in all replanted animals (weight-bearing index before transplantation: 0.499+/-0.080; 6 months after transplantation: 0.38+/-0.16) but only in two of four transplanted animals (weight-bearing index 6 months after transplantation: 0.37, 0.28, and 0.00). CONCLUSIONS: These data demonstrate the potential of joint grafting and the critical dependence of allotransplantation on the control of rejection.

Angiography↗
PubMed1997

Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in vitro stimulation with a replication-incompetent vaccinia virus encoding MART-1/Melan-A 27-35 epitope.

Active specific immunotherapy targeting tumor-associated antigens (TAA) requires reagents of high immunogenicity and safety. To address this issue, we constructed a recombinant vaccinia virus carrying a minigene insert encoding the HLA-A2.1-restricted MART-1/Melan-A27-35 melanoma TAA (rVV-M). To facilitate the entry of the antigenic epitope into the endoplasmic reticulum, a sequence coding for adenovirus E3/19K leader peptide was added. This rVV-M was made replication-incompetent by treatment with psoralen and UV light. Infection with rVV-M rendered HLA-A2.1 EBV-transformed lymphoblastoid cells sensitive to the cytotoxic effects of HLA-class-1-restricted, MART-1/Melan-A27-35-specific cytotoxic T lymphocytes (CTL). The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC). MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses. Infection with rVV-M elicited a higher CTL response than addition of exogenous peptide, whereas, when a similar protocol was used to stimulate PBMC of healthy donors, significant and specific cytotoxic activity could be observed only upon rVV-M infection but not upon exogenous peptide addition. All CTL generated upon rVV-M stimulation were also able to efficiently kill melanoma cell lines expressing both MART-1/Melan-A and HLA-A2.1. In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes. This safe and highly immunogenic reagent could be of use in TAA-targeted clinical immunotherapy.

Amino Acid Sequence↗
PubMed1997

[Tumor cachexia--a special entity and therapeutic sequelae].

Cancer cachexia as a syndrome of generalized host tissue wasting results from interactions of tumor, host and tumor-directed treatment. Cancer cachexia may be associated with all terminal cancer stages and is not tumor-specific. Weight loss, functional impairment and deterioration of the quality of life require palliation. A therapeutic algorithm based on therapeutic standards is proposed: appropriate use of parenteral and enteral nutrition, of progesterone analogues and of metoclopramide. Innovative concepts that may enable prophylactic rather than therapeutic interventions are currently under investigation.

Cachexia↗
PubMed1997

Increased surface expression of CD18 and CD11b in leukocytes after tourniquet ischemia during elective hand surgery.

The surface expression of beta2-integrins was investigated in leukocytes from patients undergoing ischemia induced by tourniquet application for elective hand surgery. Blood samples were obtained before initiation, at the end of ischemia, and after 15 minutes of reperfusion from ischemic and contralateral arms of five patients. Comparable expression of CD18, CD11a, CD11b, and CD11c could be detected by immunofluorescence in leukocytes from samples drawn from either arm before tourniquet application. In contrast, a significant increase in the expression of CD18 was detectable in monocytes, granulocytes, and lymphocytes from the ischemic arm compared with that in the nonischemic contralateral control, at the end of the ischemia time (80 +/- 16 minutes). A significantly increased expression of CD11b, but not CD11a or CD11c, determinants was also observed in granulocytes and monocytes. Concomitantly, a significant reduction in the percentages of granulocytes in samples from ischemic areas was detectable. After 15 minutes of reperfusion, differences in the expression of these adhesion molecules were no longer significant. The expression of the genes encoding interleukins IL-1alpha, IL-1beta, and IL-6 and tumor necrosis factor alpha (TNFalpha) proinflammatory cytokines was also studied by reverse polymerase chain reaction (rPCR) in peripheral blood mononuclear cells (PBMCs) obtained from the same samples in three patients. IL-1beta or IL-6 gene expression was never observed. Expression of IL-1alpha and TNFalpha genes, as detected in two patients, was not related with induction of ischemia. However, in these patients expression of one or both these genes was observed in samples derived from the ischemic but not the control arm after 15 minutes of reperfusion. These data document that overexpression of adhesion molecules and sequestration of leukocytes take place following short ischemia times, as routinely applied clinically for minor surgical procedures.

Adult↗
PubMed1997

Kinetics of high-energy phosphates in allopurinol-pretreated ischaemic and post-ischaemic skeletal muscle: an in vivo magnetic resonance spectroscopy study.

Allopurinol (AP) protects skeletal muscle function against ischaemia-induced injury, but the mechanism is not yet clear. As AP acts as a competitive xanthine oxidase inhibitor, both a reduction of oxygen-derived free radicals and an enhancement of purine resynthesis (salvage pathway) might be involved. We investigated the in vivo kinetics of high-energy phosphates in skeletal muscle after AP pretreatment using 31P-magnetic resonance spectroscopy during 2 h of ischaemia and 3 h of reperfusion in rat hindlimbs. Three animals (group A) were pretreated with a total of 160 mg/kg AP i.p., 3 control animals (group B) received the same amount of 0.9% saline solution. ATP decreased to 18.6 +/- 1.3% of the pre-ischaemic value in group A and to 17.3 +/- 2.8% in group B after 2 h of ischaemia, and rose to only 47.7 +/- 1.5 and 50.5 +/- 1.8%, respectively, after 3 h of reperfusion. Phosphocreatine fell to 7.2 +/- 2.9 and 7.6 +/- 2.2% of pre-ischaemic values after 2 h of ischaemia and rose again to 36.5 +/- 12.9 and 45.4 +/- 20.4% after 3 h of reperfusion. Inorganic phosphate (Pi) increased 5-fold after 2 h of ischaemia, irrespective of the treatment. After 3 h of reperfusion, Pi was still 4 times the pre-ischaemic value. The kinetics of ATP, PCr, and Pi levels were not statistically different between the two groups. These results indicate that the ATP salvage pathway does not play an important role in AP-induced attenuation of ischaemia/reperfusion-induced muscle damage.

Adenosine Triphosphate↗
PubMed1997

Heterogeneity of melanoma antigen-1 (MAGE-1) gene and protein expression in malignant melanoma.

OBJECTIVE: The authors' objective is to identify MAGE-1 tumor antigen in clinical melanoma specimens and to verify the extent of its expression in tumors where evidence of specific gene transcripts can be obtained. BACKGROUND DATA: The MAGE-1 gene encodes a tumor-associated antigen that can be recognized by specific cytotoxic T lymphocytes. Transcription of the MAGE-1 gene has previously been demonstrated in various malignancies, but the production of the specific gene product and its distribution in neoplastic tissues have not yet been addressed. METHODS: Total cellular mRNA was extracted from six melanoma biopsies, reverse-transcribed and tested in 25-45 cycles of reverse polymerase chain reaction (rtPCR) in the presence of primers' pairs specific for the beta-actin-positive control gene and for the MAGE-1-encoding gene. Concurrently, portions of these specimens were lysed and probed for MAGE-1 protein by immunoblotting. Additional material from the same biopsies was analyzed following immunohistological staining with MAGE-1-specific monoclonal antibodies. RESULTS: MAGE-1 gene transcription could be demonstrated following 25 cycles of rtPCR in one out of six biopsies and in three more following 35 cycles of rtPCR. 2/6 samples were negative even after 45 cycles of rtPCR. MAGE-1 protein production could be detected by immunoblotting in the lysates from biopsies showing evidence of specific gene transcription. Cells positive for MAGE-1 protein expression could be identified by immunohistochemistry on snap-frozen sections in three of the four tumors displaying specific transcripts. Distribution of positivity ranged between focal cellular areas and single positive cells in the different tumors. CONCLUSIONS: The MAGE-1 tumor antigen can be detected by specific monoclonal antibodies in clinical tumor specimens. The pattern of positivity observed in samples showing evidence of MAGE-1 gene expression suggests a relevant heterogeneity regarding MAGE-1 antigen production within individual tumor specimens.

Antibodies, Monoclonal↗
PubMed1997

Quantitative monitoring of blood supply to knee joint transplants in dogs.

BACKGROUND: Transplantation of vascularized knee joints has become technically feasible, but graft rejection as well as failures of the vascular anastomoses remain critical hazards. We therefore tested the potential of repetitive non-invasive duplex sonography to detect changes of the arterial blood flow following canine knee joint transplantation. METHODS: Four transplantations and, as controls, 4 replantations of intact canine knee joints were performed. The follow-up was 6 months. During this period, repetitive duplex sonography measurements as well as tests of knee joint function were performed. Six months postoperatively, angiographies were performed and all joints were explanted for histological investigation. RESULTS: The luminal diameters of the implanted popliteal artery remained constant in the transplanted animals (preop. 2.6 +/- 0.2 mm, 6 months postop. 2.7 +/- 0.2 mm) but decreased in the autografted controls (preop. 2.9 +/- 0.3 mm, postop. 2.0 +/- 0.3 mm). The time-averaged velocity of the popliteal artery blood flow decreased in both groups 1 month postoperatively. Subsequently, blood flow velocity recovered in transplanted animals but remained low in replanted controls. Significant arterial wall thickening was also detected in transplanted animals as compared to controls. Six months postoperatively, hypervascularization of transplanted joints was confirmed by angiography and thickening of the arterial wall by histology. Furthermore, histology identified mild to chronic allograft rejection in all transplanted joints in spite of controlled cyclosporin A trough level immunosuppression. CONCLUSIONS: Chronic rejection of transplanted vascularized knee joints appears to be associated with vessel wall thickening and hypervascularization rather than with vascular rarefaction (picture of the 'arbre mort') that is characteristic of the rejection of most parenchymatous organs. Duplex sonography appears to be sensitive in detecting the corresponding changes of blood supply.

Angiography↗