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Biomedical subjects

M Prager

Publications and source records attributed to M Prager.

At least 19 recordsLinked to original sources

Fresh arterial homograft transplantation: a novel concept for critical limb ischaemia.

INTRODUCTION: homografts have been used since the early days of vascular surgery, but have failed to provide long-term success. Arteries supplying organ transplants seldom show signs of biodegradation. We therefore introduced fresh arterial homograft repair with consecutive immunosuppression (ATX). AIM: to assess feasibility and clinical usefulness of ATX. SETTING: university teaching hospital. MATERIAL AND METHOD: conduits were harvested during multi-organ procurement and stored in Custodiol. Implantation followed immediately. Viability of the transplant was documented in all cases. Patients received immunosuppression for the duration of bypass function. RESULTS: thirteen patients received ATX for critical limb ischaemia (M/F: 11/2, age: 62yr, previous revascularisations: 4.5 (1-8), median run-off index 5, previous organ transplant: n=2. Most bypasses were anastomosed to single tibial or pedal vessels. There was no early failure. Within an average follow up of 12 months there were 6 graft thromboses in 5 patients, successfully revised in 4. Three limbs were lost after 2, 5 and 6 months due to graft failure. Graft rejection was shown in 1 out of 3 explanted grafts. CONCLUSION: we report a concept, which may circumvent the problem of biologic graft degeneration. Limb salvage was possible in 75% at 12 months in otherwise difficult circumstances.

Adolescent↗

Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a PPAR-gamma-independent manner.

PPARgamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPARgamma-ligands, 15-deoxy-delta12,14 prostaglandin-J2 (15d-PGJ2), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC- 1). Expression of PPARgamma in HMEC-1 was confirmed by RT-PCR. Both PPARgamma-ligands tested induced the activation of PPAR, but the potency of ciglitazone was higher, as evidenced by luciferase assay. Resting HMEC-1 released about 150 pg/ml of IL-8 protein. Treatment with LPS increased the IL-8 secretion up to 1 ng/ml. 15d-PGJ2 potently and dose-dependently increased both the steady-state and LPS-induced generation of IL-8 mRNA and IL-8 protein. In contrast, neither basal nor LPS-elicited expression of IL-8 was influenced by ciglitazone. We conclude, that 15d-PGJ2 is a potent inducer of IL-8 production and can be a mediator of inflammatory response, but this effect is independent of PPARgamma activation.

Cell Line↗

Collagen versus gelatin-coated Dacron versus stretch polytetrafluoroethylene in abdominal aortic bifurcation graft surgery: results of a seven-year prospective, randomized multicenter trial.

BACKGROUND: A prospective randomized multicenter trial was performed to compare knitted gelatin-coated Dacron bifurcation grafts, knitted collagen-coated Dacron grafts, and stretch polytetrafluoroethylene (PTFE) grafts. METHODS: Between 1991 and 1998, 315 elective patients were randomized by age, gender, diabetes, runoff, indication (aneurysm, aortoiliac occlusive disease), and nicotine consumption at 3 centers of vascular surgery in Austria. The patients received gelatin-coated Dacron (GEL-D) grafts (n = 109), collagen-coated Dacron (COL-D) grafts (n = 100), or stretch PTFE grafts (n = 106). RESULTS: No intraoperative deaths occurred. The 30-day mortality was 3%. No difference was found between the 3 graft materials in long-term patency. The primary 5-year patency rates were 92% for GEL-D, 89% for COL-D, and 91% for stretch PTFE (P =.6001). The secondary 5-year patency rates also differed: 97% for GEL-D, 100% for COL-D, and 97% for stretch PTFE (P =.2062). Early occlusions were observed overall in 3% and late occlusions in 5% of patients. When both Dacron grafts were compared collectively with stretch PTFE, a difference was found in infection rate: Dacron 3% (6/209) versus PTFE 0% (0/106); P <.03. CONCLUSIONS: The bifurcation grafts of all 3 materials were comparable in primary and secondary patency rates, incidence of false aneurysms, and rate of perioperative complications. Graft infections were confined to the 2 Dacron grafts and did not occur in stretch PTFE grafts.

Aorta, Abdominal↗

Prostaglandin E1 reduces ischemia/reperfusion injury by normalizing nitric oxide and superoxide release.

To test the effects of prostaglandin E1 on 2.5 h of ischemia followed by 2 h of reperfusion, continuous nitric oxide measurements (electrochemical) were correlated with intermittent assays of superoxide and peroxynitrite levels (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus muscle. Administering prostaglandin E1 (1 microg/kg) before or during ischemia/reperfusion caused normalization of the release of nitric oxide, superoxide, and peroxynitrite to slightly above preischemic levels. This pattern was dramatically different from that observed during ischemia/reperfusion alone, where nitric oxide concentration increased three times above its basal level. Normalization of constitutive nitric oxide synthase activity in the presence of prostaglandin E1 was associated with a significant reduction of superoxide and peroxynitrite production and subsequent reduction of ischemia/reperfusion injury. At 2 h of reperfusion, vasoconstriction associated with ischemia/reperfusion injury was eliminated, and edema was significantly mollified but still apparent. Prostaglandin E1 treatment does not directly inhibit constitutive nitric oxide synthase, like the inhibitor N(omega)-monomethyl-L-arginine. Some phenomenon associated with ischemia turns on endothelial constitutive nitric oxide synthase to start transforming L-arginine and oxygen into nitric oxide, but prostaglandin E1 seems to inhibit this phenomenon. Thus, essential local L-arginine pools are not depleted, and normal basal levels of essential nitric oxide are maintained, whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient constitutive nitric oxide synthase is prevented.

Acetylcholine↗

[Abdominal vascular surgery emergencies: abdominal aortic aneurysm, acute mesenteric ischemia--indications, technique, results].

Ruptured infrarenal aortic aneurysms and mesenteric ischemia are abdominal emergency situations, which should be treated by vascular surgeons. Modern means of patient transport and specialized emergency centers make it possible to bring patients suspect of having a ruptured aneurysm or a mesenteric ischemia to experienced clinics. Indication for surgery in case of symptomatic or ruptured aortic aneurysms is doubtless absolute. If there is suspicion for a ruptured aneurysm, emergency operation is indicated. In patients having undergone emergency surgery for a ruptured aneurysm of the infrarenal aorta, hospital mortality was 41%. The initial indication for surgery for patients with mesenteric ischemia usually is the "acute abdomen". Mostly only the patient's history reveals the suspicion for this disease. There are no valid radiologic examinations for proving or ruling out mesenteric ischemia. Most of our patients had arterial embolism (64%) as a source of mesenteric ischemia, followed by arterial thrombosis (28%), venous thrombosis (3%) and non-occlusive ischemia (5%). Monitoring of levels of serum lactate can be an additional tool for decision making, if a second look operation is discussed. The key for surgical success with these critically ill patients is shortening of the interval between the first symptoms of the patient and the start of surgical therapy.

Aged↗

[The value of fine-needle aspiration biopsy (FNAB) in the differential diagnosis of the "cold" thyroid nodule].

INTRODUCTION: According to the literature, fine needle aspiration biopsy (FNAB) should be the first line test to assess thyroid nodules. The value of fine needle aspiration biopsy in the differential diagnosis of "cold" thyroid nodules is discussed. METHODS: 105 consecutive patients undergoing surgery for solitary cold nodule or a dominant cold nodule in multinodular goiter and having a preoperative fine needle aspiration biopsy, are analysed. RESULTS: The cytologic results were benign in 48 cases, malignant in 8 cases and indeterminate (follicular neoplasia) in 29. Twenty biopsies were inadequate. Excluding inadequate and indeterminate biopsy results and calculating microcarcinomas (as incidental findings) as "true negative", sensitivity was 56%, specify 94% and accuracy 88%. There was a negative predictive value of 92% and a positive predictive value of 63%. CONCLUSIONS: Fine needle aspiration biopsy is helpful as an additional test. The indication for surgery for a "cold" thyroid nodule must be established in conjunction with clinical findings and other investigation procedures.

Adolescent↗

[Management of severe infection complicating aortofemoral grafts].

OBJECTIVE: Infection of the retroperitoneum after implantation of an abdomino-femoral aortic graft remains one of the main problems in vascular surgery. On basis of a critical review of own experiences we evaluated the management of this difficult clinical situation. PATIENTS: From 1970-1996 1500 aortofemoral graft operations (aneurysmal disease: 512, aortoiliacal occlusive disease: 988) were performed. Abdominal infection occurred in 12 patients (0.8%) (12 men, median age 60.5 [48-80] years). RESULTS: The median interval between operation and infection was 17.7 (0.5-108) months. The port of infection was in 50% the groin, 25% suffered from abdominal infection, in 3 cases it was not to identify. Clinical manifestation of infection was aortoduodenal fistula in 2 patients, false aneurysms in 2 cases, and a paraprosthetic abscess in another 4 patients. Operative therapy comprised (partial) removal of infected material in 10 patients with consecutive extraanatomical reconstruction in 8 of these. Mortality of graft infection was 50%. Causes of death were untreatable sepsis in 4 patients, another 2 died from hemorrhagic shock. 3 out of 6 surviving patients finally lost their limbs following multiple vascular procedures. CONCLUSION: Adequate surgical therapy of infected aortofemoral grafts remains an unsolved problem. Lack of knowledge of suitable parameters for the best treatment leaves the outcome of prosthetic infection unpredictable. Removal of the infected graft with extraanatomic reconstruction seems to be the standard of surgical treatment, which is recommended in these cases.

Aged↗

Effect of melatonin on activated macrophage TNF, IL-6, and reactive oxygen intermediates.

Melatonin has recently been investigated as a biological response modifier in sepsis and hypovolemic shock. Although melatonin is reported to influence a variety of inflammatory and immune responses, evidence supporting its effects on important macrophage-derived mediators is incomplete. This study was designed to determine whether melatonin alters the release TNF, IL-6, and reactive oxygen intermediates by activated macrophages. TNF and IL-6 bioactivity in LPS-stimulated Wistar rat alveolar macrophage and RAW 264.7 cell culture supernatants were unchanged by pretreatment with melatonin. Similarly, macrophage production of reactive oxygen intermediates, including H2O2 and superoxide anion, were unaffected by melatonin pretreatment. PMA-stimulated H2O2 production was determined in rat alveolar macrophages and RAW 264.7 cells. Superoxide anion generation was determined in the rat alveolar macrophage NR8383 cell line. Melatonin, at concentrations ranging from 10(-7) to 10(-4) M, does not alter LPS-stimulated TNF and IL-6, or PMA-stimulated H2O2 and superoxide anion production by the macrophage populations studied. These observations are in contrast to previous reports. Further studies are necessary to determine whether melatonin indirectly influences macrophage function by actions on nonmacrophage cell populations.

Animals↗

[Abdominal aortic aneurysm: surgery, indications, technique, outcome].

The fate of a patient with an abdominal aortic aneurysm] (AAA) is influenced by the risk of rupture and embolism. When the indication for operation is considered, individual associated risk factors have to be taken into account. With regard to the literature, the following recommendations concerning indication for surgery can be given: emergency surgery for symptomatic or ruptured aneurysm; elective surgery: aneurysms 5 cm diameter or growing AAA 5 mm/year, patient with acceptable individual risk for operation; asymptomatic aneurysms less than 5 cm in diameter, without growth in patients aged over 75 years and/or considerable perioperative risk should not be operated on: sonography should be done 3-monthly as a continuing control. Finally the results in our institution are presented for elective surgery: 30-day mortality 3.5%, AAA with rupture, no shock: 20%, ruptured AAA with shock 47%, respectively.

Aortic Dissection↗

[Acute mesenteric ischemia].

UNLABELLED: Acute mesenteric ischemia is a life-threatening vascular emergency. A retrospective analysis of our patients was performed to describe the development of the various procedures of diagnostic assessment and treatment between 1970 and 1996, to show the influence on survival and to define recent standards. PATIENTS: Between 1970 and 1996, 145 patients, 75 male and 70 female, suffering from acute mesenteric ischemia, have been treated at the Department of Surgery-University Hospital Vienna. RESULTS: In most cases AMI was caused by arterial embolism (64.1%, n = 93) followed by arterial thrombosis (27.6%, n= 40). Venous thrombosis (3.5%, n = 5) and non-occlusive AMI (4.8%, n = 7) were rare events. Serum lactate level has been determined routinely in all patients having been admitted with acute abdomen since 1984 and turned out to be positive in 81.2% (mean value 9.81 (3.21-22.3) mmol/l). Abdominal x-ray gave only in some individual cases special hints to the advanced intestinal gangrene. Abdominal sonography led to the correct diagnostic assessment in 52 patients (= 35.8%). Angiography was in 92% conclusive for the diagnosis. Abdominal CT led to establish the correct diagnosis in > 80%. Our series with revascularisation (thrombectomy/embolectomy or bypass) has resulted in 73.8% patient survival with intestine having been maintained in the most favourable cases. CONCLUSIONS: Early diagnostic assessment and treatment are decisive for survival. Abdominal-CT, angiography and serum-lactate constitute quick and reliable means to provide diagnosis and to judge the stage of AMI in addition to meticulous examination of patients' history, symptoms and physical conditions.

Acute Disease↗

Acute-phase hepatocytes regulate liver sinusoidal cell mediator production.

BACKGROUND: Overproduction of liver sinusoidal cell (LCS) mediators in response to endotoxemia or gram-negative infection that follows tissue injury may contribute to hepatic dysfunction. OBJECTIVE: To better define the role of hepatocyte-derived acute-phase reactants in the regulation of sinusoidal cell mediator production following sequential insults, we tested the hypothesis that interleukin-6 (IL-6) prestimulation alters hepatocyte regulation of lipopolysaccharide (LPS)-stimulated sinusoidal cell tumor necrosis factor (TNF), IL-6, and nitric oxide production. METHODS: Hepatocytes and LSCs were isolated from Wistar rats, and in vitro responses were compared between LSCs alone and hepatocyte-LSC cocultures. Cocultures and LSCs alone were sequentially stimulated with IL-6 (5000 U/mL) then LPS (dose-response), and culture supernatants were analyzed for TNF (L929 cytolysis), IL-6 (7TD1 proliferation), and nitric oxide (Griess reaction). Induction of acute-phase protein synthesis by the stimulation of hepatocytes with IL-6 and dexamethasone (0.1 mumol/L) was assayed by methionine radiolabeling and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Coculture levels of messenger RNA for TNF-alpha and IL-6 were examined by RNA extraction and reverse transcriptase polymerase chain reaction with specific primers. RESULTS: Interleukin-6 and dexamethasone signal hepatocyte acute-phase protein synthesis. Prestimulation of cocultures, but not of LSCs alone, with IL-6 inhibits LPS-stimulated IL-6 and nitric oxide production significantly. Bioactivity of TNF is reduced to a lesser extent. Polymerase chain reaction analysis demonstrated similar levels of TNF and IL-6 message following sequential stimulation. CONCLUSIONS: Interleukin-6-stimulated acute-phase hepatocytes limit LPS-stimulated coculture cytokine bioactivity and nitric oxide production. This hepatocyte response may provide a local counterregulatory mechanism to limit LSC-mediated injury.

Acute-Phase Proteins↗

Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle myocytes.

Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. To determine whether NO production can be induced in skeletal muscle, we stimulated C2C12 mouse skeletal muscle myocytes with putative inducers of nitric oxide synthase (NOS). Neither lipopolysaccharide (LPS), interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF), nor interferon-gamma (IFN) was able to stimulate nitrite production by C2C12 cells when administered alone. However, combinations of IFN with either TNF or IL-1 resulted in significant nitrite production; simultaneous stimulation of cells with all three cytokines resulted in significantly increased nitrite production compared with any combination of two cytokines. Northern analysis of RNA obtained from stimulated C2C12 cells revealed induction of a single mRNA band that precisely coincided with the mRNA band of mouse macrophage-inducible NOS (iNOS). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis followed by sequencing of the 5' 765 bases of the skeletal muscle iNOS cDNA demonstrated exact homology with mouse macrophage iNOS. These findings indicate that combinations of cytokines stimulate NO production in skeletal muscle cells via induction of the macrophage-type iNOS gene.

Amino Acid Oxidoreductases↗

[Surgical therapy of acute thrombosis of leg-pelvic veins].

A series of 213 consecutive patients suffering from acute iliofemoral vein thrombosis who underwent venous thrombectomy is analyzed. Surgery was performed from an inguinal approach with a Fogarty-balloon-catheter from the proximal vessel and by bimanual exprimation from the femoral and popliteal veins. Post-operative oral anticoagulation treatment was attempted whenever possible. Long term results obtained in 130 patients after a median follow-up of 78 months (44% free of symptoms, 33% PTS [postthrombolic syndrome] I, 15% PTS II, 8% PTS III) showed a significant correlation to the duration of preoperative anamnesis: < or = 5 days: 64% free of symptoms, > 5 days: 34% free of symptoms, the rate of PTS III was equally distributed in the group with long (< or = 5 days) and short (> 5 days) anamnesis (8 and 9% respectively). Postoperative Dicumarol-therapy decreased the rate of severe PTS: 28% without, respectively 10% with therapy. If the medication was cancelled aggravation of the clinical symptoms in 1 third of the patients was observed. Venous thrombectomy is an important treatment option in patients with contraindications to thrombolytic therapy. With patients younger than 65 years and short anamnesis functional results are acceptable, high risk patients (severe cardiac disease and previous pulmonary embolism) should be treated with medical therapy only.

Female↗

Thermoregulatory responses to hyperthermia during isoflurane anesthesia in humans.

The authors tested the hypotheses that isoflurane anesthesia increases the threshold for sweating but minimally decreases the gain (sensitivity) or maximum intensity of this response and that thermoregulatory responses to hyperthermia are similar in anesthetized men and women. Sweating in response to core hyperthermia was studied in five men and five women during 0, 0.8, and 1.2% end-tidal isoflurane anesthesia. Thigh sweating was quantified by measuring gas flow, relative humidity, and temperature passing over a known surface area. The distal esophageal temperature triggering sweating was considered the sweating threshold, and gain was defined as the core temperature increment required to increase sweating rate from 25 to 75% of maximum observed intensity. The sweating threshold increased linearly with isoflurane concentration from 36.6 +/- 0.1 to 38.1 +/- 0.1 degrees C in the men and from 37.1 +/- 0.3 to 38.3 +/- 0.2 degrees C in the women. The thresholds were significantly higher in women than in men. Gain and maximum sweating intensities were similar at each anesthetic concentration and in men and women. These data indicate that isoflurane anesthesia significantly increases the threshold triggering thermoregulatory sweating but that gain and maximum sweating rate are relatively well preserved.

Anesthesia↗

A decade of oral anticoagulant treatment to maintain autologous vein grafts for femoropopliteal atherosclerosis.

To determine whether long-term oral anticoagulant treatment was effective in improving graft performance and preventing major amputation following vein bypass surgery for femoropopliteal atherosclerosis, a clinical trial was conducted in one single center and continued during 10 years. After 130 patients had electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group (treatment with phenprocoumon [n = 66]) or to a control group (n = 64) that remained without any anticoagulant treatment. Primary end points of the study were graft reocclusion and limb loss. The median durations of primary patency and limb salvage were significantly longer for treated patients than that for controls. In addition, survival in the therapy group was longer. Following autologous vein bypass surgery in the treated group, the results were superior in terms of graft patency, limb salvage, and survival.

Administration, Oral↗

Dacron versus polytetrafluoroethylene for Y-aortic bifurcation grafts: a six-year prospective, randomized trial.

BACKGROUND: A prospective, randomized trial was conducted to compare Dacron with expanded polytetrafluoroethylene (ePTFE) in reconstructive aortoiliac surgery. No comparable trial with a prospective, randomized design with a comparable number of patients or an equal long-term follow-up period can be found in the literature. METHODS: Between 1984 and 1989, 165 patients were randomized for either Dacron or ePTFE on the basis of age, sex, indication for surgery, diabetes, nicotine consumption, runoff, and operative approach. The two groups were well matched for randomization criteria, as well as the incidence of aneurysms. RESULTS: No statistically significant difference was found between the two graft materials in terms of patency rates (corrected 3-year patency rates: Dacron = 95% vs ePTFE = 95%; Breslow, p = 0.83; Mantel-Cox, p = 0.74). Subgroup analysis comparing long-term patency rates of the two graft materials and relating them to poor runoff, good runoff, aneurysms, and arterial occlusive disease also failed to show any significant differences between ePTFE and Dacron. Early graft failure (n = 6; 3.6% of the patient population; p = 0.045) and severe abdominal graft infection (n = 3; 1.8% of the total population) were seen only in ePTFE grafts. However, these did not affect the corrected long-term patency rate of ePTFE grafts. There were five late graft failures with PTFE (3.0%) and four with Dacron (2.4%). CONCLUSIONS: Graft materials currently available for aortoiliac repair were comparable in terms of corrected long-term patency rates. The alleged advantages of PTFE were not confirmed by our data. PTFE grafts were associated with a higher rate of complications, and more redo operations were required to duplicate the results obtained with Dacron.

Aorta↗