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Biomedical subjects

H Probst

Publications and source records attributed to H Probst.

At least 19 recordsLinked to original sources
PubMed2006

[New treatments in vascular diseases].

In superficial venous insufficiency, surgery remains the treatment of choice. Endovenous therapies are a minimal invasive alternative, whose long-term results are not demonstrated yet. In the treatment of abdominal aortic aneurysm, endovascular repair (EVAR) and laparoscopic approach are comparatively studied with open repair, to define their precise indications. In occlusive arterial disease, endovascular treatment offers inferior results in term of durability and patency, however with a decrease in morbidity and mortality.

Humans↗
PubMed2006

[Quality of life after superficial femoral vein harvest for infra-inguinal reconstructions].

BACKGROUND: The superficial femoral vein (SFV) is a well-established alternative conduit for infra-inguinal reconstructivenous hypertension after SFV harvest may however result in significant morbidity. This study reports the efficiency of SFV as conduit for infra-inguinal reconstructions and characterize the anatomic and physiologic changes in harvest limbs and their relationship to the development of venous complications. METHODS: From May 1999 through November 2003, 23 SFV were harvested from 21 patients undergoing infra-inguinal reconstructions. Bypasses were controlled by regular duplex-ultrasound. The venous morbidity was assessed by measurements of leg circumferences, strain-gauge plethysmography and quality of life, investigated by the VEINES-QOL scale. RESULTS: At a mean follow-up of 10.4 months (range 1-56), primary, secondary patency and limb salvage rates of infra-inguinal bypasses using SFV are 71.4%, 76.2% and 85.7% respectively. No patient had major venous claudication. Oedema was significantly present in nine patients. Strain-gauge plethysmography showed outflow obstruction in all patients. The VEINES-QOL assessment showed no limitation in social and domestic activity, moderate complain about leg heaviness despite presence of oedema. CONCLUSION: The SFV harvest is a reliable conduit for infra-inguinal reconstructions and results in moderate venous morbidity in terms of functional consequences and quality of life.

Aged↗
PubMed2006

Moving to a high-tech approach to the irradiation of early breast cancer: is it possible to balance efficacy, morbidity and resource use?

There is substantial evidence documenting the potential morbidity associated with radiotherapy in early breast cancer. An appraisal of current standard radiation practice is therefore necessary, given that women are surviving longer, have an improved quality of life, and are overcoming subsequent side-effects caused by postoperative irradiation. New technology allows the application of more complex approaches. This discussion paper considers some of the benefits of the widespread use of new complex approaches, such as intensity-modulated radiotherapy (IMRT) in the light of staffing and equipment shortfalls, and possible consequences on waiting times for treatment. The discussion is considered under the following themes: (1) which women with breast cancer benefit from complex treatment approaches? (2) What is the role of treatment accuracy in limiting morbidity? And (3) what is the potential effect of complex breast irradiation approaches on service delivery? In the UK, and globally, many departments are struggling to meet waiting-time guidelines. The use of more complex approaches for breast irradiation may increase this difficulty. However, a number of simple technical changes can be used to enhance efficacy and reduce levels of normal tissue morbidity. A sub-set of women who are at greatest risk from normal tissue morbidity or reduced cosmesis should be accurately defined in order to allow departments to plan their treatment strategies with optimal use of resources.

Breast Neoplasms↗
PubMed2006

Clinical results of autologous infrainguinal revascularization using grafts originating distal to the femoral bifurcation in patients with mild inflow disease.

AIM: Chronic critical limb ischemia (CLI) often requires venous bypass grafting to distal arterial segments. However, graft patency is influenced by the length and quality of the graft and occasionally patients may have limited suitable veins. We investigated short distal bypass grafting from the superficial femoral or popliteal artery to the infrapopliteal, ankle or foot arteries, despite angiographic alterations of inflow vessels, providing that invasive pressure measurement at the site of the planned proximal anastomosis revealed an inflow-brachial pressure difference of <or=10 mmHg. METHODS: Four hundred and twenty-three consecutive infrainguinal bypass grafts were performed for CLI between June, 1999 and November, 2002 at our institution. All patients underwent preoperative clinical examination, arteriography and assessment of the veins by duplex ultrasound. The study group are patients in whom the proximal and distal anastomoses of the bypass are below the femoral bifurcation and the popliteal artery, respectively. Invasive arterial pressure measurements were recorded at the level of the planned proximal anastomosis which was performed at that level if the difference of the inflow-brachial pressure was <or=10 mmHg, irrespective of angiographic alterations of the inflow vessels proximal to the planned anastomosis. All patients had a clinical follow-up included a duplex examination of their graft, at 1 week, 3, 9 and 12 months and, thereafter, annually. No patient was lost to follow-up. RESULTS: Sixty-seven patients underwent 71 short distal bypass grafts in 71 limbs with reversed saphenous vein grafts in 52, in situ saphenous veins in 11, reversed cephalic vein in 1 and composite veins in 7, respectively. Surgical or endovascular interventions to improve inflow were required in 4 limbs (5.6%). The mean follow-up time was 22.5 months and the two-year survival was 92.5%. Primary and secondary patency rates at 2 years were 73% and 93%, respectively, and the limb salvage rate was 98.5%. CONCLUSION: In appropriately selected patients, short distal venous bypass grafts can be performed with satisfactory patency and limb salvage rates even in the presence of morphologic alterations of the inflow vessels providing that these are not hemodynamically significant, or can be corrected intraoperatively.

Aged↗
PubMed2004

Comparative assessment of intimal hyperplasia development after 14 days in two different experimental settings: tissue culture versus ex vivo continuous perfusion of human saphenous vein.

BACKGROUND: Intimal hyperplasia (IH) is a vascular remodeling process which often leads to failure of arterial bypass or hemodialysis access. Experimental and clinical work have provided insight in IH development; however, further studies under precise controlled conditions are required to improve therapeutic strategies to inhibit IH development. Ex vivo perfusion of human vessel segments under standardized hemodynamic conditions may provide an adequate experimental approach for this purpose. Therefore, chronically perfused venous segments were studied and compared to traditional static culture procedures with regard to functional and histomorphologic characteristics as well as gene expression. MATERIALS AND METHODS: Static vein culture allowing high tissue viability was performed as previously described. Ex vivo vein support system (EVVSS) was performed using a vein support system consisting of an incubator with a perfusion chamber and a pump. EVVSS allows vessel perfusion under continuous flow while maintaining controlled hemodynamic conditions. Each human saphenous vein was divided in two parts, one cultured in a Pyrex dish and the other part perfused in EVVSS for 14days. Testing of vasomotion, histomorphometry, expression of CD 31, Factor VIII, MIB 1, alpha-actin, and PAI-l were determined before and after 14days of either experimental conditions. RESULTS: Human venous segments cultured under traditional or perfused conditions exhibited similar IH after 14 days as shown by histomorphometry. Smooth-muscle cell (SMC) was preserved after chronic perfusion. Although integrity of both endothelial and smooth-muscle cells appears to be maintained in both culture conditions as confirmed by CD31, factor VIII, and alpha-actin expression, a few smooth-muscle cells in the media stained positive for factor VIII. Cell-proliferation marker MIB-1 was also detected in the two settings and PAI-1 mRNA expression and activity increased significantly after 14 days of culture and perfusion. CONCLUSION: This study demonstrates the feasibility to chronically perfuse human vessels under sterile conditions with preservation of cellular integrity and vascular contractility. To gain insights into the mechanisms leading to IH, it will now be possible to study vascular remodeling not only under static conditions but also in hemodynamic environment mimicking as closely as possible the flow conditions encountered in reconstructive vascular surgery.

Culture Techniques↗
PubMed2003

Hypoxia-induced cell death in human malignant glioma cells: energy deprivation promotes decoupling of mitochondrial cytochrome c release from caspase processing and necrotic cell death.

Hypoxia induces apoptosis in primary and transformed cells and in various tumor cell lines in vitro. In contrast, there is little apoptosis and predominant necrosis despite extensive hypoxia in human glioblastomas in vivo. We here characterize ultrastructural and biochemical features of cell death in LN-229, LN-18 and U87MG malignant glioma cells in a paradigm of hypoxia with partial glucose deprivation in vitro. Electron microscopic analysis of hypoxia-challenged glioma cells demonstrated early stages of apoptosis but predominant necrosis. ATP levels declined during hypoxia, but recovered with re-exposure to normoxic conditions unless hypoxia exceeded 8 h. Longer hypoxic exposure resulted in irreversible ATP depletion and delayed cell death. Hypoxia induced mitochondrial release of cytochrome c, but there was no cleavage of caspases 3, 7, 8 or 9, and no DNA fragmentation. Ectopic expression of BCL-XL conferred protection from hypoxia-induced cell death, whereas the overexpression of the antiapoptotic proteins X-linked-inhibitor-of-apoptosis-protein and cytokine response modifier-A had no effect. These findings suggest that glioma cells resist adverse effects of hypoxia until energy stores are depleted and then undergo necrosis rather than apoptosis because of energy deprivation.

Adenosine Triphosphate↗
PubMed2002

Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions.

We report our experience in percutaneous treatment of non-tumoral superior vena cava syndrome (SVCS) between December 1998 and July 2001. During a period of 2.5 years, 9 patients (age range 27-84 years, mean age 50 years) were treated percutaneously for significant non-tumoral SVCS. Symptomatic SVCS were due to dialysis catheters (7), central line (1) and radiation therapy (1). In thrombotic occlusions and severe stenosis, a preliminary in situ thrombolysis was achieved before angioplasty. Patients were followed by echo-Doppler, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or phlebography. Complete recanalization of the veins and immediate resolution of symptomatic SVCS were obtained in all patients, with no procedure-related complication. Thirteen stents were placed in 9 patients with a mean clinical follow-up of 9.1 months (range 2-23 months). One hundred percent patency at 6 months was obtained. Two patients recurred twice and were treated with new stent placement. At 12 months the patency was 67% and assisted patency was 100%. Stent placement in benign symptomatic SVCS is a safe and minimally invasive procedure, with no technical and clinical complications in our experience. It allowed immediate relief of symptoms, and in dialysed patients could provide continued use of hemodialysis access. Close clinical surveillance is mandatory to assess stent patency.

Adult↗
PubMed2001

Oxygen-dependent regulation of in vivo replication of simian virus 40 DNA is modulated by glucose.

Simian virus 40 (SV40)-infected CV1 cells exposed to hypoxia show an inhibition of viral replication. Reoxygenation after several hours of hypoxia results in new initiations followed by a nearly synchronous round of SV40 replication. In this communication, we examined the effect of glucose on inhibition of viral DNA replication under hypoxia. We found that glucose stimulated SV40 DNA replication under hypoxia in two different ways. First, the rate of DNA synthesis, i.e. the fork propagation rate, increased. This effect seemed to be mediated by inhibition of mitochondrial respiration by glucose (Crabtree effect). Inhibition of mitochondrial respiration probably resulted in a higher intracellular oxygen concentration and an activation of oxygen-dependent ribonucleotide reductase, which provides the precursors for DNA synthesis. This glucose effect was consequently strongly dependent on the strength of hypoxia and the extent of intracellular respiration; hypoxic gassing with 10 ppm instead of 200-400 ppm O(2) or treatment of hypoxic cells with a mitochondrial uncoupler (carbonyl cyanide m-chlorophenylhydrazone) reduced the glucose effect on replication, whereas antimycin A, an inhibitor of respiration, increased it. The second effect of glucose concerned initiation, i.e. stimulation of unwinding of the viral origin. This effect was not influenced by the strength of hypoxia or the extent of cellular respiration and seemed, therefore, not to be mediated through a Crabtree effect. No evidence for a direct correlation between the cellular ATP concentration and the extent of SV40 replication under hypoxia was found. The effect of glucose on replication under hypoxia was not restricted to SV40-infected CV1 cells but was also detectable in HeLa cells. This suggests it to be a mechanism of more general validity.

Adenosine Triphosphate↗
PubMed2001

[Revascularization of the diabetic foot].

Diabetes is an important risk factor for atherosclerosis. The diabetic foot is characterised by the association of arteriopathy and neuropathy. The vascular damage associates a non-occlusive microangiopathy and a macroangiopathy. The first principles of treatment are the control of pain, of an eventual infection, and the restoration of pulsatile blood flow in case of ischemia. Angiologic investigation must be undertaken, as well as an arteriography, in order to plan the revascularisation. The treatment options are angioplasty with or without stenting and surgery. Distal reconstructions with anastomosis to the leg or pedal arteries have a satisfactory limb-salvage rates. This aggressive and systematic approach to the diabetic foot is economically sound, allows hope for limb salvage and improves the quality of life.

Angiography↗
PubMed2001

[Value of the "sleeve" resection for pulmonary cancers].

A sleeve resection is an anatomical pulmonary resection (segmentectomy, lobectomy or pneumonectomy) combined with the excision of a bronchial segment, with the anastomosis between the airway proximal and distal to it. This technique allows a certain number of centrally located tumors to be completely resected with sufficient margins of healthy tissue. Thus it is possible that the rest of the involved lung can be spared (sleeve segmentectomy or lobectomy), or a pneumonectomy can be performed despite invasion of the carina or distal trachea. The comparison of series of sleeve and conventional resections shows similar 5-year survival rates if the stage and histological subtypes are taken into account. The specific morbidity of the procedure is the partial or complete breakdown of the anastomosis (producing a stenosis or a bronchopleural fistula). This is uncommon and can usually be prevented by the use of a protective perianastomotic flap.

Humans↗
PubMed1999

Hypoxia blocks in vivo initiation of simian virus 40 replication at a stage preceding origin unwinding.

Simian virus 40 (SV40)-infected CV1 cells transiently exposed to hypoxia show a burst of viral replication immediately after reoxygenation. DNA precursor incorporation and analysis of growing daughter strands by alkaline sedimentation demonstrated that SV40 DNA synthesis began with a lag of about 3 to 5 min after reoxygenation followed by a largely synchronous viral replication round. Viral RNA-DNA primers complementary to the SV40 origin region were not detectable before 3 min upon reoxygenation. A distinct form of circular closed, supercoiled SV40 DNA was detectable as soon as 3 min after reoxygenation but not under hypoxia. Sensitivity to the DNA nuclease Bal 31 and migration behavior in chloroquine-containing agarose gels suggested that this DNA species was highly underwound compared to other SV40 topoisomers and was probably related to the highly underwound form U DNA first described by Dean et al. (F. B. Dean, P. Bullock, Y. Murakami, C. R. Wobbe, L. Weissbach, and J. Hurwitz, Proc. Natl. Acad. Sci. USA 84:16-20, 1987), in vitro. 3'-OH ends of presumed RNA-DNA primers could be detected in form U by 3' end labeling with T7 polymerase. Addition of aphidicolin to the cells before reoxygenation led to a pronounced accumulation of form U DNA containing RNA-DNA primers. In vivo pulse-chase kinetic studies performed with aphidicolin-treated SV40-infected cells showed that form U is an initial intermediate of SV40 DNA replication which matures into higher-molecular-weight replication intermediates and into SV40 form I DNA after removal of the inhibitor. These results suggest that in vivo initiation of SV40 replication is arrested by hypoxia before origin unwinding and primer synthesis.

Animals↗
PubMed1999

Fast control of DNA replication in response to hypoxia and to inhibited protein synthesis in CCRF-CEM and HeLa cells.

In order to elucidate whether data about the fast regulation of DNA replication in dependence on oxygen supply and on a functioning protein synthesis, previously elaborated with Ehrlich ascites cells, are valid for human cells too, we repeated key experiments with CCRF-CEM and HeLa cells. The most important techniques employed were DNA fibre autoradiography and alkaline sedimentation analyses of growing (pulse-labeled) daughter strand DNA. It was found that CCRF-CEM and HeLa cells responded to transient hypoxia and to transient inhibition of protein synthesis in an almost identical fashion. Scheduled replicon initiations were reversibly suppressed and the progress rates of replication forks, which were already active before the respective inhibitory conditions were established, were reversibly slowed down. The inclusion of the fork progress rate in the response differs from Ehrlich ascites cells, which respond only by suppressing initiation. Further circumstances of the fast oxygen dependent response, concerning the behaviour of ribonucleotide reductase and of the dNTP pools, revealed no significant differences among the three cell lines. The striking identity of the response of each of the cell lines to hypoxia and to inhibited protein synthesis prompts the suspicion that converging fast regulatory pathways act on the cellular replication machinery. The phenomena as such seem to be rather widespread among mammalian cells.

Autoradiography↗
PubMed1997

[Treatment of myocardial infarction by primary PTCA within 12 to 24 hours after onset of pain].

BACKGROUND AND OBJECTIVE: The time elapsed until effective infarct vessel perfusion has been identified as an essential determinant of survival after acute myocardial infarction (MI). Significant mortality rate reduction has not been demonstrated for patients who received thrombolytic treatment more than 12 to 24 hours after MI. For this reason such patients have so far largely been denied reperfusion treatment and have thus been excluded from any potential benefit of an reopened infarct vessel. It was the aim of this study to assess the applicability and safety of achieving reperfusion by percutaneous transluminal coronary angioplasty (PTCA) without prior thrombolysis (primary PTCA) within 12 (> 12) to 24 (< or = 24) hours after onset of pain, taking into account early and late results in selected consecutive patients. PATIENTS AND METHODS: The data were analysed retrospectively of 35 patients (29 men, 6 women; mean age 60 [49-78] years) who had been admitted and treated by primary PTCA for MI more than 12-24 hours after onset of pain, with persisting ECG changes and (or) continuing chest pain. Reperfusion rates, acute haemodynamic parameters, acute cardiac and noncardiac complications, 30-day mortality rate, 3-month angiographic results and late mortality rate were obtained after an average of 23 (4-36) months. RESULTS: Complete infarct vessel reperfusion was achieved in 30 patients (85.7%), the infarct vessel remaining occluded in five. The early measurement of mean left ventricular ejection fraction was 53% (8-76%). A small, conservatively managed pericardial effusion occurred in one patient due to coronary artery penetration. Three patients who were in cardiogenic shock on admission died (8.6% 30-day mortality rate). Nine cases of restenosis and two of re-occlusion of the infarct vessel were documented in 24 patients who were investigated invasively 3 months after the primary PTCA. One patient had sustained a nonfatal MI. During the follow-up period one patient died of a noncardiac cause. INTERPRETATION: In this selected group of patients who received treatment more than 12 to 24 hours after MI primary PTCA achieved a high rate of reperfusion, while early and late complications were rare. Using individualized criteria of patient selection, primary PTCA can accomplish recanalization. The question of prognostic advantage can only be answered by results in a larger and randomized cohort of patients.

Aged↗
PubMed1997

Role of ribonucleotide reductase and deoxynucleotide pools in the oxygen-dependent control of DNA replication in Ehrlich ascites cells.

Cultured Ehrlich ascites cells were exposed to different oxygen tensions (ranging from nearly complete anoxia to 95% O2 at 10(5) Pa) and to transient (5-10 h) hypoxia (0.02% O2 at 10(5) Pa). Treated cells were examined with respect to the intracellular concentration of the M2-specific tyrosyl free radical of ribonucleotide reductase by EPR spectroscopy, and with respect to the pool sizes of all four deoxynucleoside triphosphates by an enzymatic assay employing DNA polymerase I of Escherichia coli. From 2% to 0.02% O2, the free radical level decreased continually from a normal value to just above detectability by the EPR measurement employed, and quickly recovered when hypoxic cells were resupplied with atmospheric O2. Concurrently, analogous changes of the size of the dCTP pool occurred, whereas the pool sizes dATP and dGTP underwent no changes, and the size of the dTTP pool only moderate changes. The changes of the free radical concentration and of the dCTP pool correlated well with the suppression or reactivation of DNA replication under the respective O2 conditions. The results consistently support the hypothesis of a fast-acting regulatory pathway that controls the rate of DNA replication in proliferating cells according to sufficient availability of O2. Therefore, ribonucleotide reductase may serve, in addition to providing DNA building blocks, as a pO2 sensor, which transmits the signal in the form of an altered intracellular dCTP concentration, directly or indirectly, to the nuclear-replication machinery.

Animals↗
PubMed1996

Increasing the work speed of radiographers: the effect on the accuracy of a set-up of a complex shaped cranial field, part of a matched cranio spinal junction.

Simulator port films of 22 set-ups of a complex cranial field positioned by radiographers working either at normal or at increased pace were compared with a control film. Analysis showed that accuracy decreased for set-ups achieved at an increased speed, demonstrating risks to treatment outcomes incurred by increasing working speed to meet workload demands.

Cerebellar Neoplasms↗
PubMed1995

Split course radiotherapy for bladder cancer in elderly unfit patients.

Between 1980 and 1987, 89 patients with T1-T4 carcinoma of the bladder were treated with a split course of external beam radiotherapy. All patients were felt to be unsuitable for a prolonged course of radical radiotherapy because of age and/or poor general health. The intention was to provide local control. The majority of patients were treated with 10-12 fractions, with a mean dose of 45 Gy (range 31.5-57.7), within a mean overall time of 48 days. Of the 89 patients only 62 were assessable with a median follow-up of 110 months (range 64-157). In the remainder, poor health, poor performance status, or early (< 3 months) death did not allow assessment of tumour control. Complete remission was achieved in 28/89 (31%) patients. This was highly dependent on T stage: 56% T1/T2, 30% T3a/T3b, 5% T4. Median survival for patients with Stage T1/T2, T3a/T3b and T4 disease was 22, 10 and 8 months respectively. Acute grade 1-2 radiation reactions occurred in 60% of these patients, and only 5/62 (8%) experienced grade 2-3 late complications, assessed according to the RTOG scoring system. No patient had more severe treatment related morbidity.

Adult↗
PubMed1995

[Successful high frequency current catheter ablation of an accessory conduction pathway in the "neck region" of a coronary sinus aneurysm. A case report].

In this case report the electrophysiological findings in a 24 year old female patient are demonstrated. For about 12 years she suffered from recurrent atrioventricular reentrant tachycardia with a rate of 230 beats per minute. Electrophysiological study resulted in diagnosis of a posteroseptal accessory pathway. Ablation was attempted primarily from a left ventricular access, but the pathway could not be reached from this position. After contrasting the coronary sinus a large coronary sinus aneurysm could be diagnosed. The accessory pathway was located in the "neck"-region of the aneurysm. By application of radiofrequency current in this location the bypass tract could be ablated. This case report shows that accessory pathways in coronary sinus aneurysms can be ablated without complications in this location.

Adult↗