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E Uhl

Publications and source records attributed to E Uhl.

At least 55 records · Page 3Linked to original sources

Dural arteriovenous fistulas including the transverse and sigmoid sinuses: results of treatment in 30 cases.

We report about the treatment and outcome of 30 patients with dural arteriovenous fistulas including the transverse and sigmoid sinuses treated between 1986 and 1995. All patients underwent panangiography for definitive diagnosis. The dAVF were supplied by the external carotid artery system alone (14 patients), both external and internal carotid systems (10 patients) or both anterior and posterior circulation (6 patients). Depending on the venous drainage the fistulas were classified following a modification of Djindjian's description with 18 patients revealing Type I (main sinus with antegrade flow), 5 Type II a (main sinus with reflux into the contralateral sinus). 5 Type II b (cortical veins), 1 Type II a+b (both) and 1 of Type III (direct cortical drainage). Bruit, pulsatile tinnitus and headaches were the most common symptoms. 6 patients presented with intracranial haemorrhage, 4 with progressive neurological deficit or seizures and 3 with dementia. Arterial embolization was performed in all cases except one, where a transvenous approach for balloon occlusion of the transverse sinus was performed. 21 patients were treated by single or repeated embolization alone. Only in 9/21 cases did arterial embolization result in complete occlusion of the fistula. In 12/21 patients incomplete occlusion was achieved. Following embolization 8 patients underwent additional surgery including coagulation of the feeding arteries and arterialized veins, sinus resection and reconstruction of the sinus. Overall, 18 patients were cured, 11 improved and 1 patient was unchanged. There was a total number of 5 complications including transient stroke, transient facial nerve palsy, and a small necrotic skin area following embolization. Venous infarction of the occipital lobe was induced by transvenous occlusion and surgical resection of the transverse sinus in one patient each, respectively. From our results we conclude that the endovascular therapy alone is the treatment of choice in case of Type I fistulas. In dAVF of Type II and III repeated endovascular treatment seems not to be sufficient and additional surgery is necessary.

Adolescent↗

Ischemia increases the angiogenic potency of basic fibroblast growth factor (FGF-2).

The aim of this study was to investigate the angiogenic response to exogenously administered basic fibroblast growth factor (FGF-2) in normal and ischemic skin, using the hairless mouse ear microcirculatory model. The hairless mouse ear is a well-established model for in vivo studies of skin microcirculation. Using this model, angiogenesis- and angiogenesis-associated changes in the microcirculation can be directly and continuously viewed and quantified in a variety of different experimental settings. To create ischemia in the mouse ear, all but one of the three to four feeding vessels nourishing the ear were ligated 3 days prior to a local subdermal injection of FGF-2 (9.3 + 1-0.5 mm/mm2) or saline into the dorsum of the ears. Angiogenesis was quantified by direct observation, at high magnification, of the injection site where increases in total vessel length (TVL) were measured repeatedly over 18 days following injection. We found a significant (P < 0.01) increase in TVL in normal and ischemic ears injected with FGF-2. Saline injection also induced a significant increase in TVL in ischemic ears. However, the angiogenic response to FGF-2 in ischemic ears was significantly stronger than saline alone in ischemic ears or saline or FGF-2 in normal ears. This response could be used clinically to accelerate angiogenesis and thus increase perfusion in ischemic tissue.

Animals↗

Protective effect of the somatostatin analogue octreotide in ischemia/reperfusion-induced acute pancreatitis in rats.

Somatostatin and its stable analogue octreotide are proposed to ameliorate the outcome from acute pancreatitis by inhibiting pancreatic secretion and preventing cell injury. This study investigated the effect of somatostatin analogue octreotide on pancreatic microcirculatory injury (by means of intravital fluorescence microscopy) and enzyme release after ischemia/reperfusion of the pancreas in rats. Octreotide, injected 15 min before the end of 2 h of ischemia as a bolus injection (50 micrograms kg-1 i.v.) or as a continuous infusion (50 micrograms kg-1 h-1 i.v.), attenuated postischemic reperfusion injury of the pancreas as evidenced by a significant (p < 0.05) improvement in capillary perfusion and decrease in leukocyteendothelium interaction in postcapillary venules compared to ischemia without treatment. Pancreas amylase concentration remained unchanged in the octreotide group but increased significantly (p < 0.05) in the ischemia group. These results indicate a protective effect of octreotide against postischemic reperfusion injury of the pancreas in rats.

Acute Disease↗

Expression and localization of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumoral growth.

In addition to its well-known homoeostatic actions in the cardiovascular system, ET-1 has been shown to constitute a potent growth regulatory peptide in various tissues. We have studied the expression of ET-1 and its receptors (ET-Ar and ET-Br) in human meningiomas (n = 35) as well as their involvement in cellular growth. By PCR of reverse-transcribed RNA we detected ET-1 mRNA in 91% (32 of 35), ET-Ar mRNA in 82% (29 of 35), and ET-Br mRNA in 42% (15 of 35) of human meningiomas examined. The localization of ET-1 mRNA, ET-Ar mRNA, and ET-1 peptide in tumoral cells was observed by in situ hybridization and immunohistochemistry, whereas ET-Br mRNA was expressed at low level only in cells belonging to blood vessels. In addition, we found that ET-1 stimulated [3H] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist for ET-Ar. In contrast, RES-701-3, an antagonist of ET-Br, did not block the proliferative effect of ET-1. In conclusion, our data provide evidence that ET-1 constitutes an important growth factor for meningiomas acting via ET-Ar. We can hypothesize that ET-1, acting in concert with other growth factors and cytokines, is involved in the meningioma tumorigenesis.

Adult↗

Improvement of skin flap perfusion by subdermal injection of recombinant human basic fibroblast growth factor.

The effect of subcutaneously injected recombinant human basic fibroblast growth factor (bFGF) was studied in an arterial skin flap model on the ear of the hairless mouse. Fifty-three male, hairless mice were randomly assigned to 4 groups and pretreated in two different time intervals with different doses of human bFGF. Microvascular perfusion of the skin flaps was determined over a 5-day period by means of intravital microscopy after intravenous injection of the fluorescence marker fluorescein isothiocyanate-dextran (M(r) 150,000). Human bFGF (2,700 ng) injected 6 days before flap creation could not improve perfusion of the flap (n = 10) when compared with controls. However, when applied 18 days before flap creation (n = 13), the same dose resulted in a significant reduction of nonperfused tissue at day 5 after flap creation (12.3% vs 26.8%, p < 0.01). Eighteen-day pretreatment with 1,200 ng (n = 10) and 480 ng (n = 10) had no significant effect on skin flap perfusion. We conclude, therefore, that successful pretreatment with bFGF for prevention of skin flap necrosis is time and dose dependent.

Animals↗

Hyperbaric oxygen improves wound healing in normal and ischemic skin tissue.

The influence of hyperbaric oxygen on reepithelialization and on microvascular perfusion of wounds in normal and ischemic skin tissue was investigated by using a standardized model, in ears of hairless mice. Animals were treated within 2 hours of wound creation and then twice daily with 100% oxygen at 2 atmospheres of absolute pressure. Ischemia was induced by ligating two of the three major vessels of the ear 2.5 days before wound creation. Wound surface area was measured every third day after wound creation. In addition, microvascular blood flow before and during the wound healing process was measured by scanning the ear with a new laser Doppler perfusion imager. In normal tissue (n = 13), hyperbaric oxygen therapy significantly accelerated wound healing by 2 days (p < 0.01) as compared with controls (n = 16). In ischemic tissue (n = 16), treatment with hyperbaric oxygen reduced time for reepithelialization in control animals (n = 16) from 14.3 to 9.9 days (p < 0.001). Laser Doppler data showed no difference in tissue blood flow between treated and untreated animals. In comparison with normal tissue, wound healing in ischemic tissue was characterized by a reduced and less intense hyperemic response. These data suggest that hyperbaric oxygen therapy improves reepithelialization in normal and ischemic skin tissue. The beneficial effect is not associated with changes in microvascular perfusion and therefore is probably due to high arteriolar oxygen content and oxygen diffusion.

Animals↗

Leukocyte rolling in venules of striated muscle and skin is mediated by P-selectin, not by L-selectin.

Leukocyte rolling in post-capillary venules is mediated by adhesion molecules of the selectin family expressed on both leukocytes (L-selectin) and endothelial cells (E- and P-selectin). With the use of intravital fluorescence microscopy, the effects of antibodies against these selectins were analyzed in the skinfold chamber model of BALB/c mice and the ear model of homozygous hairless mice (hr/hr) that permit chronic observation of striated muscle and skin microcirculation in awake animals, respectively. Mice were injected intravenously with monoclonal antibodies (MAb) to murine L-selectin and E-selectin and affinity-purified polyclonal antibodies to P-selectin. The antibodies, which are known to block cell adhesion, were tested by immunoprecipitation to selectively bind to L-, E-, or P-selectin. Leukocyte rolling was a constant finding in both microcirculation models in the absence of inflammatory stimuli. In both models, injection of anti-P-selectin antibodies completely prevented baseline leukocyte rolling over an observation period of 2 h (P < 0.01 vs. baseline), while no effects were seen after administration of either anti-L-selectin or anti-E-selectin MAb. Treatment with the isotype-matched control antibodies did not affect leukocyte rolling in either model. We conclude that leukocyte rolling in postcapillary venules of murine striated muscle and skin is a physiological process mediated via P-selectin, whereas L- and E-selectin appear not to play a significant role under these circumstances.

Animals↗

Basic fibroblast growth factor accelerates wound healing in chronically ischaemic tissue.

The influence of subcutaneously injected recombinant human basic fibroblast growth factor (bFGF) on wound healing in normal (n = 20) and ischaemic (n = 28) skin tissue was investigated. Standardized wounds (5 mm2) were created on the ears of hairless mice and treated for the first 3 days after wound creation with total doses of 720 ng (n = 24) and 4050 ng (n = 24) bFGF. The bFGF had no effect on wound healing in non-ischaemic tissue. In ischaemic skin, mean(s.d.) wound surface area after treatment with 720 ng bFGF was 1.6(0.9), 0.5(0.6) and 0.1(0.3) mm2 compared with 2.8(1.0), 1.4(1.0) and 0.8(0.7) mm2 for control wounds on days 7 (P < 0.04), 10 (P < 0.03) and 13 (P < 0.04) respectively. High-dose bFGF (4050 ng) reduced the mean(s.d.) wound surface area to 2.4(0.7) and 0.8(0.7) mm2 compared with 3.9(0.6) and 2.1(0.8) mm2 for control wounds on days 7 (P < 0.006) and 10 (P < 0.02) respectively. These results suggest that bFGF may be of use for the treatment of wounds in ischaemic tissue.

Animals↗

A new model for studying microcirculatory changes during dermal wound healing.

Intact blood supply by microcirculation to a wounded site is an indispensable prerequisite for normal tissue regeneration. However, microvascular changes taking place in the healing process of skin wounds are not understood due to the fact that only few models allow chronic in vivo studies on skin microcirculation. Therefore, we have modified the hairless mouse ear model with the purpose of a quantitative in vivo study of microhemodynamic changes throughout the healing process. Following the creation of a standardized skin wound on the ear of the homozygous hairless mouse (hr/hr), microvessel diameters, red blood cell velocities, wet weight, and leucocyte content of the ear tissue were determined. Surface area of the wound was assessed until complete closure was achieved. By repeated measurements at identical sites over the entire healing period, a distinct pattern of microvascular changes could be observed: microvessel diameters increased to a maximum a few days after wound creation, whereas red blood cell velocities reached their highest values at a later point in time and were still elevated after complete reepithelization of the wounds. Edema and leucocyte content of the ear tissue was most prominent in the early healing phase and gradually decreased to normal values thereafter. These results demonstrate changes of the microvasculature of the hairless mouse ear to injury, which are in accordance to other more indirect studies on this topic. Therefore, we conclude that the model presented is suitable for prolonged quantitative analysis of microcirculation during normal wound healing and may be used to assess microvascular changes taking place during wound healing in pathologically altered tissue.

Animals↗

Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection.

During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.

Animals↗

The hairless mouse ear for in vivo studies of skin microcirculation.

The homozygous (hr/hr) hairless mouse ear was introduced in 1980 by Eriksson and coworkers as a model for in vivo studies of the skin microcirculation. Herein we expand on this work, presenting results of in vivo microvascular parameter measurements and morphologic studies in the intact ear. The in vivo measurements include microvascular diameter, RBC velocity, capillary density, and the frequency and amplitude of arteriolar vasomotion. In connection with the in vivo studies, a detailed anatomic description of the overall and vascular anatomy is given. Additionally, the preparation techniques for carrying out these in vivo and morphologic studies in the mouse ear are presented in detail.

Animals↗