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Biomedical subjects

T Hupp

Publications and source records attributed to T Hupp.

At least 19 recordsLinked to original sources

Pedal bypass for limb-threatening ischaemia: an 11-year review.

Fifty-six patients with limb-threatening ischaemia had pedal revascularization with either autologous vein (n = 39) or sequential composite graft with a 6-mm polytetrafluoroethylene prosthesis and autologous vein (n = 17); 75 per cent had gangrene and skin necrosis and 25 per cent had ischaemic rest pain alone. Twelve grafts occluded within the first week, and resulted in major amputation in eight patients after unsuccessful revision. Two patients required amputation for persistent ischaemia despite a patent bypass. One patient died from bowel perforation (2 per cent). In 47 (84 per cent) of the 56 patients limb and life were preserved. The primary patency rate after 1, 2 and 4 years was 65, 55 and 55 per cent respectively, the secondary patency rate was 71, 62 and 62 per cent, and cumulative limb salvage rates were 77, 71 and 66 per cent. Life-table survival rates during follow-up (median 25 (range 0-112) months) were 89, 78 and 52 per cent respectively after 1, 2 and 4 years. Thirteen of 21 patients who died during follow-up did not require major amputation. Pedal reconstruction with autologous vein provides limb salvage until death in nearly two-thirds of patients with critical limb ischaemia resulting from crural arterial occlusive disease.

Adult

Exercise activates renal dysfunction in hypertension.

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.

Antihypertensive Agents

A direct effect of activated human p53 on nuclear DNA replication.

p53 is a transcriptional activator and repressor, but recent evidence suggests that some of its many biological functions may not be dependent on transcription. To determine whether p53 exerts a direct influence on nuclear DNA replication, purified human p53 was added to a transcription-free DNA replication extract from Xenopus eggs. Full-length human p53 that inhibits SV40 DNA replication in vitro had no effect on nuclear DNA synthesis in the Xenopus system. In contrast, a C-terminal truncated form of p53 (p53 delta 30), which is constitutively active for DNA binding and similar to an alternately spliced form found in vivo, showed a concentration-dependent inhibition of DNA replication in both the soluble SV40 system and eukaryotic nuclei. This inhibition occurred primarily at initiation of DNA synthesis. Oxidation of p53 delta 30, which eliminates DNA binding activity, also abrogated the protein's ability to inhibit nuclear DNA synthesis. The p53 binding DNA consensus sequence enhanced rather than competed away inhibitory activity of p53 delta 30. Therefore, p53 that is constitutively active for DNA binding can inhibit nuclear DNA replication in the absence of transcription. This inhibition may require binding of p53 to DNA, in addition to interactions between p53 and proteins of the replication complex.

Animals

[The sonographic and computed radiographic findings in perigraft reactions after the surgical implantation of vascular prostheses].

Between January 1988 and January 1994, 24 patients with heterologous vascular bypasses were examined with suspected diagnosis of a perigraft reaction (PGR). All patients were subjected to ultrasound and CT. PGR ist defined as a sterile inflammation along the course of a vascular prosthesis. The typical clinical presentation is a fluctuating tumour with a localised painless swelling. In all cases liquid formations could be confirmed by diagnostic imaging procedures; signs of infection could be excluded. The synopsis of the clinical presentation, the time interval after implantation of the prosthetic material and the signs of sonography and CT can reliably exclude infection of the prosthesis and confirm the diagnosis of a PGR.

Aged

[Endovascular and open reconstructive surgery of renal artery lesions].

Besides antihypertensive drug treatment and reconstructive surgery, the percutaneous transluminal angioplasty became an established treatment modality for renal artery stenosis since the late 70's. The treatment aimed at curing the renovascular hypertension, at normalizing and improving of both compensated and decompensated renal insufficiency in order to avoid prolonged hemodialysis after acute renal failure. Endovascular procedures contributed significantly to reach a normotensive state, particularly in cases with renal artery stenosis concomitant with fibromuscular dysplasia and gives similar results as open surgical methods if certain morphological features are considered. However, surgery is generally more effective than endoluminal treatment when all forms of renal artery stenosis are considered together. This holds true in particular for ostial stenosis, complete obstruction of the renal artery, aneurysms and a multitude of rare renovascular diseases. Surgery should be first line treatment to preserve or improve the renal function. According to the pertinent literature, endovascular methods should be considered first for the treatment of renovascular hypertension. Despite the frequent repetition of potential advantages of PTA, a first direct comparison of both modalities demonstrated better primary results after surgical treatment. Even the total cost were similar since PTA requires frequent follow-up with short intervals necessitating secondary interventions.

Angiography

Repeat exercise renograms in hypertension identify persistent renal dysfunction.

BACKGROUND: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology. OBJECTIVE: To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible. DESIGN: We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy. RESULTS: The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results. CONCLUSION: The results are considered relevant, because a direct relationship appears probable between hypertension and the disturbance investigated. Reproducible results suggest that the exercise-mediated disturbance is fixed to the kidneys, that it can be reactivated repeatedly and that it may play a role in maintaining hypertension.

Antihypertensive Agents

[Determination of the degree of stenosis of the internal carotid artery in the surgical specimen after eversion TEA: comparison with angiography and c-w-Doppler ultrasound].

UNLABELLED: 22 carotid specimens following eversion-endarterectomy were compared with preoperative assessment of carotid stenosis obtained angiographically and by c-w-Doppler-sonography. The intact, unsplit specimens were perfused with a liquid plastic material (Palavit M). After hardening of the plastic material the specimens were removed. The local degree of carotid stenosis with respect to diameter reduction was assessed by direct measurement of the plastic specimens at the narrowest site compared with the diameter of the carotid eversion specimens at the place of the maximum stenosis. The distal degree of carotid stenosis was assessed by comparison of the diameter of the distal internal carotid artery obtained intraoperatively with the measurements of the plastic specimens (1 mm vascular wall thickness of distal internal carotid artery was taken into account). RESULTS: Both the local and the distal degree of carotid stenosis diameter (mean 84.7% +/- 8.4% and 82.1% +/- 9.1% respectively) were underestimated in the preoperative angiogram (79.8 +/- 9% by ECST-criteria and 69 +/- 10.3% by NASCET-criteria) in most of the cases. The difference of the diameter reduction was statistically significant (p < 0.05 and p < 0.01 respectively, Wilcoxon signed rank test). The c-w-Doppler assessments were 82.6 +/- 8.2% (n.s.). CONCLUSION: Our results suggest that the preoperative assessment of internal carotid stenosis obtained angiographically or by c-w-Doppler-sonography easily underestimate the true degree of carotid stenosis.

Adult

[Dystopic goiter--aspects of definition and surgical therapy].

The incidence in the literature of dystopic goiter depends on classification of the false endothoracic goiter ("substernal goiter") as dystopic and varies from 2 to 20%. From November 1989 through April 1993 we operated on 530 patients with benign nodular goiters. In 84 patients (15.8%) the operation proved a dystopic goiter. We showed that difficulties in comparing our data with published series were due to misnomers of the dystopic goiter. The dystopic goiter comprises the true endothoracic goiters (alliata vera and isolata vera) as well as the false endothoracic goiters (substernal goiter). The precise classification of the dystopic goiter is crucial to an optimal operative strategy reducing postoperative morbidity.

Adolescent

The role of the p53 protein in the apoptotic response.

When mammalian cells or tissues are exposed to DNA damaging agents a programmed cell death pathway is induced as well as a cell cycle arrest. In mice in which the p53 gene has been inactivated by homologous recombination this response is profoundly diminished. These mice develop normally so that developmentally induced apoptotic events do not require p53. The p53 gene product is a 393 amino acid nuclear protein that binds specifically to DNA and can act as a positive transcription factor. High levels of p53 can induce the transcription of gene products involved in the cell cycle arrest and apoptotic pathway. The p53 proteins activity is very tightly controlled both by allosteric regulation of its DNA binding function and by regulation of the protein's stability. These results are discussed in the context of the mutations in p53 found in human tumours and their implications for the treatment of the disease by the use of radiation and chemotherapeutic agents that target DNA.

Allosteric Regulation

Revision of the proximal aortic anastomosis after aortic bifurcation surgery.

The implantation of an aortic bifurcation graft (ABG) for treatment of occlusive (OD) and aneurysmal (AD) aortoiliac disease is a standard technique with good long-term results and a relatively low incidence of complications. In a retrospective review of our patients from 1964 to 1993 only 36/1520 patients were identified who required reoperation at the proximal aortic anastomosis after ABG. Indications were graft occlusion (15/36) and graft stenoses (2/36), refractory to graft thrombectomy, proximal aortic anastomotic aneurysms (11/36) or graft infection (8/36). Graft occlusion or stenosis most frequently led to aortic reoperation in the OD-group (53.5%), recurrent aneurysmal disease (37.5%) and graft infection (37.5%) were the dominant indications in the AD-group. Mean time interval to reoperation was shorter in cases of graft infection (35 +/- 33 months) as compared with graft stenosis (66 +/- 58 months), graft occlusion (86 +/- 49 months) or aortic anastomotic aneurysms (152 +/- 90 months). Of the reoperations, 92% were done electively, 8% as emergency procedures. The perioperative course was uneventful in 67% of patients. Overall mortality rate after elective revisional surgery was 3% but reached 66% in emergencies. Postoperative morbidity and mortality was related to preoperative morbidity and the urgency of surgery, not with the mode of aortic intervention nor indication.

Anastomosis, Surgical

[Diagnosis and therapy of perioperative lung embolism].

Pulmonary embolism is a major cause of postoperative problems, accounting for 12-20% postoperative deaths. 0.1% to 0.4% of all hospitalised patients die due to acute pulmonary embolism. Thus, pulmonary embolism should be included in the differential diagnostic considerations. Blood gas analysis, ECG, chest roentgenography, scintigraphy, pulmonary arterial catheterisation, echocardiography, digital subtraction angiography, and angiography are important diagnostic tools. When pulmonary embolism is not life-threatening, heparinisation may be an adequate therapeutic approach. In the case of severe cardiovascular instability, recanalisation of the pulmonary arterial tree has to be achieved. Recent studies show that preceding surgery may not be an absolute contraindication to thrombolysis. Recommendations for thrombolytic therapy include the bolus administration of 250,000 U of urokinase followed by a continuous infusion of 40-60,000 U per hour. In an emergency situation, a bolus dose of 1-2,000,000 U may be administered. A neurosurgical operation in the preceding 10 days is still considered an absolute contraindication to thrombolysis. Patient outcome in the case of cardiopulmonary resuscitation for massive pulmonary embolism may be improved by the bolus application of 2-3,000,000 U of urokinase. In addition or alternatively, mechanical thrombus fragmentation via catheter or surgical embolectomy may be used in certain hospitals.

Angiography, Digital Subtraction

[Nonocclusive intestinal ischemia as a complication of hemodialysis treatment].

A 52-year-old man on haemodialysis treatment for chronic glomerulonephritis also had a nephrotic syndrome, hypercholesterolaemia, severe arterial hypertension and peripheral vascular disease in stage IIb. He also was a heavy smoker. Following a nonspecific diarrhoeal illness, which caused haemoconcentration, he developed abdominal pain and fever. WBC count (29,000/microliter) and serum lactate level (18.2 mmol/l) were elevated, and there were clinical signs of lower abdominal peritonitis. Laparotomy revealed multiple ischaemic segments. The arteries were not thrombosed but had severe atheromatous changes. There is an increasing incidence of such nonocclusive intestinal ischaemia because there are more elderly people and more patients with high-risk factors among those requiring dialysis.

Chronic Disease

Tumour suppressor genes and molecular chaperones.

The two tumour suppressor genes that are most commonly inactivated in human cancer are the p53 gene on chromosome 17 and the retinoblastoma (Rb) gene on chromosome 11. Recent studies of both gene products suggest that they are able to act as powerful negative regulators of cell division. The Rb gene seems to exert this activity by physically complexing to a variety of specific transcription factors and inactivating their function. The capacity of Rb protein to bind these factors is regulated by phosphorylation. The Rb protein can therefore be seen to act as a chaperone for these factors. The p53 protein also may act in part by regulating transcription but may also interact directly with the DNA replication apparatus. The growth suppressive function of p53 is induced by DNA damage leading to an attractive model of p53 as an essential checkpoint control. The p53 protein interacts with members of the hsp70 chaperone family which we now show can regulate its function.

Genes, Retinoblastoma

Renovascular hypertension: a perfusion disturbance that escaped recognition.

A bilateral, exercise-mediated, hippurate transport disturbance was previously described when patients with fixed renovascular hypertension were imaged with o-iodo-hippurate. This study sought to test the hypothesis that patients with an abnormal exercise scintigram have a perfusion abnormality characterized by dysregulation of renal blood flow. We imaged 23 patients with hypertension and angiographically documented renovascular disease in the supine position, as well as during upright exercise. Seven normotensive volunteers served as controls. We measured the resting glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) with a single compartment radiotracer infusion clearance. The clearance examination also included a measurement period with 25 watt ergometric exercise. Nine hypertensive patients had normal exercise renograms. These patients had age-appropriate clearance values at rest and during exercise, as well as age-appropriate best-organ (generally without stenosis) GFR and ERPF values. The filtration fraction (FF) was 0.21 at rest and 0.22 during exercise. Fourteen hypertensive patients had a bilateral, exercise-induced disturbance of hippurate transport. In these patients, the global resting GFRs and ERPFs were decreased 40% from age-appropriate predicted values. The FF remained at 0.20. Light exercise caused a pronounced contraction of GFR and a less severe reduction in the ERPF. During exercise the mean filtration fraction was only 0.12. The exercise-induced reduction in the clearance values was bilateral, which indicated that the perfusion of nonstenosed organs was compromised as well. We suggest that the described perfusion abnormality occupies a relevant position during the maintenance phase of fixed renovascular hypertension.

Adult

[Animal experiment studies of carcinogen-induced tumor development in colotomies in relation to suture materials].

To assess the possible risk of cancer in the operated colon after stapling compared with vicryl sutures, the influence of the nickel-containing staples was tested in caecum-resected and carcinogen-treated rats. The nickel-containing staples were seen as a cocarcinogen. The aim of the study was to determine whether a higher incidence of cancer occurs at the anastomotic suture line depending on stapler vs. vicryl sutures after subcutaneous application of carcinogens (dimethylhydrazine). The results show that there is no increased risk of cancer following mechanical stapling.

1,2-Dimethylhydrazine