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Biomedical subjects

M Rogy

Publications and source records attributed to M Rogy.

18 recordsLinked to original sources
PubMed2001

Combined radiochemotherapy of locally advanced unresectable pancreatic adenocarcinoma with mitomycin C plus 24-hour continuous infusional gemcitabine.

BACKGROUND: In locally advanced pancreatic cancer, the combination of chemotherapy with radiotherapy is gaining increasing importance; although, in view of the reported long-term results of several contemporary trials, further improvements are certainly warranted. The aim of the present study was to evaluate the effectiveness and safety of a combined-treatment modality consisting of systemic chemotherapy with 24-h continuous infusional gemcitabine and mitomycin C, plus external beam radiotherapy in patients with localized unresectable adenocarcinoma of the pancreas. METHODS AND MATERIALS: Systemic chemotherapy consisted of mitomycin C 8 mg/m2 given as i.v. bolus injection on day 1 and gemcitabine administered as a 24-h continous infusion once weekly for 3 of 4 weeks. The starting dose of gemcitabine was 100 mg/m2 and dose levels were escalated in consecutive cohorts of 3-6 patients to 130 and 160 mg/m2, utilizing an escalating-dose Phase I trial design. Radiation therapy using megavolt irradiation (total dose, 45 Gy, 1.8 Gy/day) of 6 MV photons or greater with a 3- or 4-field technique was delivered concurrently for 5-6 weeks. RESULTS: Between January 1997 and August 1998, a total of 15 patients were enrolled in this trial, all of whom were assessable for toxicity, response, and survival. The dose-limiting toxicities at the 160 mg/m2 gemcitabine level were myelosuppression, specifically neutropenia +/- thrombocytopenia, and gastrointestinal symptoms, including stomatitis, vomiting, and diarrhea. Only 1 partial response was observed (7%), and disease was stabilized in 10 additional patients (67%). The median time to progression was 5.5 months (range, 2-12 months). Whereas all patients developed distant metastases, locoregional failure occurred in only 3. The median survival time was 8.3 months (range, 2.5 to 22.0+ months), and the 1-year survival rate was 13.3%. CONCLUSION: The MTD of gemcitabine when given as prolonged infusion in combination with mitomycin C and radiation therapy was 130 mg/m2/week. Therapeutic results suggest that combined chemoradiation with this regimen is feasible and effective for local control of pancreatic cancer, but essentially ineffective in counteracting metastatic tumor growth.

Adenocarcinoma↗
PubMed1998

Endothelial cell adhesion molecule and PMNL response to inflammatory stimuli and AGE-modified fibronectin.

BACKGROUND: Atherosclerotic vascular disease is the leading cause of death in patients with diabetes mellitus and end-stage renal disease. Advanced glycation end products (AGEs) are strongly suggested to be involved in the pathogenesis of atherosclerosis in these patients who also frequently experience infectious complications. We hypothesized that the interaction of AGEs and inflammatory mediators contributes to the up-regulation of endothelial cell activation. METHODS: We investigated the effect of advanced glycated fibronectin in the presence or absence of inflammatory stimuli on the endothelial cell surface and mRNA expression of cell adhesion molecules. Furthermore, the influence of advanced glycated fibronectin on the transendothelial migration pattern of polymorphonuclear cells was analyzed. RESULTS: Exposure to advanced glycated fibronectin together with inflammatory stimuli such as interleukin (IL)-1alpha, tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) led to a significant increase in the surface expression of the cell adhesion molecules E-selectin, ICAM-1, VCAM-1 and PECAM-1 on endothelial cells. Soluble AGEs in combination with advanced glycated fibronectin significantly enhanced the endothelial cell surface expression of ICAM-1, VCAM-1 and PECAM-1, whereas this was not the case for E-selectin. At the transcriptional level short-time exposure of endothelial cells to advanced glycated fibronectin and inflammatory mediators resulted in an increased expression of E-selectin, ICAM-1 and VCAM-1 mRNA levels, whereas PECAM-1 repeatedly showed a significant decrease of gene transcript levels. An increase of mRNA levels was also observed for E-selectin, ICAM-1, VCAM-1 and PECAM-1 following incubation with a combination of advanced glycated fibronectin and soluble advanced glycation end-products. Furthermore, polymorphonuclear cells responded with a sevenfold increase in transendothelial migration following exposure of endothelial cells to advanced glycated fibronectin and inflammatory mediators. CONCLUSIONS: These results suggest that the combination of matrix glycation and inflammation up-regulates the activation of the endothelial cell adhesion cascade, a mechanism that might contribute to the increased burden of atherosclerotic morbidity and mortality in patients suffering from diabetes mellitus or chronic renal failure.

Albumins↗
PubMed1996

Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells.

Autonomous release of hematopoietic growth factors may play a crucial role in the pathogenesis of certain hematological malignancies. Because of its cytokine synthesis-inhibiting action, interleukin 10 (IL-10) could be a potentially useful molecule to affect leukemic cell growth in such disorders. Chronic myelomonocytic leukemia (CMML) cells spontaneously form myeloid colonies (colony-forming units-granulocyte/macrophage) in methylcellulose, suggesting an autocrine growth factor-mediated mechanism. We studied the effect of recombinant human IL-10 (rhIL-10) on the in vitro growth of mononuclear cells obtained from peripheral blood or bone marrow of patients with CMML. IL-10 specifically binding to leukemic cells had a profound and dose-dependent inhibitory effect on autonomous in vitro growth of CMML cells. IL-10 significantly inhibited the spontaneous growth of myeloid colonies in methylcellulose in 10/11 patients, and autonomous CMML cell growth in suspension in 5/5 patients tested. Spontaneous colony growth from CMML cells was also markedly reduced by addition of antigranulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies, but not by addition of antibodies against G-CSF, IL-3, or IL-6, IL-10-induced suppression of CMML cell growth was reversed by the addition of exogenous GM-CSF and correlated with a substantial decrease in GM-CSF production by leukemic cells, both at the mRNA and protein levels. Our data indicate that IL-10 profoundly inhibits the autonomous growth of CMML cells in vitro most likely through suppression of endogenous GM-CSF release. This observation suggests therapeutic evaluation of rhIL-10 in patients with CMML.

Aged↗
PubMed1996

A human tumor necrosis factor p75 receptor agonist stimulates in vitro T cell proliferation but does not produce inflammation or shock in the baboon.

Tumor necrosis factor (TNF) is a potentially useful adjunct to anticancer therapies. However, the clinical utility of TNF has been limited by generalized toxicity and hypotension. Recently, studies have begun to dissect the individual proinflammatory and immunologic responses that result from TNF binding to its two cellular receptors, p55 and p75, in an attempt to develop TNF receptor agonists with reduced systemic toxicity. To evaluate a p75 receptor selective TNF mutant (p75TNF), TNF and p75TNF were administered to healthy anesthetized baboons. Intravenous infusion of the p75TNF produced none of the hemodynamic changes seen after the infusion of TNF. Infusion of p75TNF also failed to induce the plasma appearance of interleukins 6 and 8. However, p75TNF enhanced in vitro baboon thymocyte proliferation to concanavalin A, and infusion of p75TNF resulted in increased soluble p55 and p75 receptor plasma concentrations. Local skin necrosis and tissue neutrophil infiltration were seen after subcutaneous injections of TNF and p55TNF. Subcutaneous injection of p75TNF did not result in skin necrosis but did result in a modest dermal infiltration of lymphocytes and macrophages. The findings suggest that p75TNF may stimulate T cell proliferation without the systemic and local toxicity seen with TNF.

Animals↗
PubMed1996

Ciliary neurotrophic factor is catabolic and shares with IL-6 the capacity to induce an acute phase response.

Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 (IL-6) superfamily, has recently been shown to induce several inflammatory responses when administered to healthy animals, including induction of fever and a hepatic acute phase protein response. In the present report, 250 micrograms.kg body wt-1.day-1 of recombinant rat CNTF or murine IL-6 were repeatedly administered to healthy mice over a 7-day period in an effort to compare biological responses. In addition to its in vivo capacity to elicit a hepatic acute phase response, administration of CNTF, but not IL-6, produced profound anorexia and lean tissue wasting in mice. In C57B1/6 mice, 7 days of CNTF administration led to a 21% loss in carcass protein content, resulting from carcass protein breakdown rates being increased 218% over freely fed controls (both P < 0.01). Protein synthesis rates in carcass protein were also increased in CNTF-treated mice compared with both freely fed animals and mice pair-fed equivalent quantities of food. In contrast, administration of equivalent quantities of murine IL-6 had no effect on food intake or body weight in mice, although IL-6 produced a similar hepatic acute phase response, as determined by increases in serum amyloid P and seromucoid fraction and increases in total hepatic protein synthesis. However, when CNTF was coincubated with extensor digitorum longus muscles from juvenile rats in vitro, rates of total muscle and myofibrillar protein degradation and muscle protein synthesis were unchanged. We conclude that CNTF can regulate in vivo both skeletal muscle remodeling as well as the distant anorexia and hepatic acute phase protein responses. In the case of skeletal muscle, these actions are both indirect and independent of the associated anorexia. These properties of CNTF are distinct from IL-6, which when administered to the mouse at these doses is neither anorexigenic nor cachexia producing.

Acute-Phase Proteins↗
PubMed1995

Necrosectomy and laparostomy--a combined therapeutic concept in acute necrotising pancreatitis.

OBJECTIVE: To present our experience with laparostomy and necrosectomy in the treatment of acute necrotising pancreatitis, and to show how refinements in our treatment regimen improved mortality over the years despite no reduction in the severity of the disease. DESIGN: Retrospective study. SETTING: University hospital, Austria. SUBJECTS: 125 patients treated by laparostomy/necrosectomy with repeated revisions during the period January 1983 to December 1991. INTERVENTIONS: Laparostomy, blunt necrosectomy, operative lavage, and open drainage. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULTS: The severity of disease was assessed by the APACHE II score (median 15, range 4-30). In 106 of the 125 patients (85%) the necrotic pancreatic tissue was infected. Patients were operated on if they deteriorated clinically or if organ failure was suspected. A change in the protocol from revisions on demand (1983/4) to planned re-exploration at 48 hour intervals (1985/8) was associated with a reduction in mortality from 53% (16/30) to 28% (20/72). This was further reduced in 1989/91 to 17% (4/23) when a protocol of revisions planned for individual patients was introduced (p = 0.02). The incidence of gastrointestinal fistulas during the three periods was 6/30 (20%); 24/72 (33%); and 1/23 (4%); (p = 0.022), whereas that of intraabdominal bleeding remained much the same (7/23, 23%; 13/72, 18%; and 4/23, 17%; p = 0.56). The median (range) APACHE II scores for the three periods were 12 (4-27), 15 (5-30), and 14 (4-25). CONCLUSION: By continual revision of our protocol, together with accompanying improvements in intensive care, our mortality decreased significantly during the nine year period.

Acute Disease↗
PubMed1994

The metabolic effects of platelet-activating factor antagonism in endotoxemic man.

OBJECTIVE: To determine if the inflammatory phospholipid platelet-activating factor (PAF) participated in the symptomatologic, metabolic, and counterregulatory hormonal responses of human endotoxemia. DESIGN: In a double-blind, placebo-controlled study, five subjects received 10 mg of the PAF antagonist Ro 24-4736 orally, while five control subjects received a placebo. Eighteen hours later, all subjects were administered 4 ng/kg of endotoxin (lipopolysaccharide) intravenously. SETTING: The Clinical Research Center of The New York Hospital-Cornell Medical Center. PARTICIPANTS: Healthy male volunteers. MAIN OUTCOME MEASURES: Repeated measurements of vital signs, symptoms, cytokine and hormone levels, resting energy expenditure, platelet aggregation, and bleeding times were performed during a 24-hour period. RESULTS: Subjects who were pretreated with the PAF antagonist experienced fewer symptoms, including rigors at 1 hour (P < .05) and myalgias at 1 through 4 hours (P < .05) after administration of lipopolysaccharide. This was in concert with a diminished peak cortisol level (668 +/- 107 vs 959 +/- 159 nmol/L in controls; P < .05), epinephrine secretion (1057 +/- 165 vs 2029 +/- 431 nmol/L in controls; P < .05), and almost complete inhibition of PAF-induced platelet aggregation ex vivo. CONCLUSIONS: These findings in the face of unaltered circulating cytokines tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6, as well as the tumor necrosis factor receptor-I s, suggest that PAF may influence some endotoxin-induced, counterregulatory hormonal responses and symptoms through cytokine-independent mechanisms. This study further supports the role of PAF antagonists as an adjunct to cytokine blockade in the treatment of gram-negative sepsis.

Adult↗
PubMed1993

Perioperative TNF alpha and IL-6 concentrations correlate with septic state, organ function, and APACHE II scores in intra-abdominal infection.

OBJECTIVE: To find out if concentrations of tumour necrosis factor a (TNF alpha) and interleukin-6 (IL-6) play a part in the pathophysiology of intra-abdominal infection, and try to identify patients who would benefit from immunotherapy against TNF alpha. DESIGN: Prospective open study. SETTING: University hospital. SUBJECTS: 19 consecutive patients (septic shock, n = 4; sepsis syndrome, n = 6; and no sepsis syndrome, n = 9, classified by the APACHE II score and the criteria of the Methyl-prednisolone Severe Sepsis Study Group) who were to undergo their first operation for intra-abdominal infection. MAIN OUTCOME MEASURES: Correlation between median (interquartile) concentrations of TNF alpha and IL-6 (pg/ml), and APACHE II score, plasma lactate concentration, and organ function. RESULTS: Perioperative concentrations of both TNF alpha (p = 0.001) and IL-6 (p = 0.006) were significantly higher in patients with septic shock. Preoperative cardiovascular and respiratory failure were associated with significantly raised TNF alpha (p < 0.001 in both cases) and IL-6 concentrations (p = 0.02 and p < 0.001, respectively). The preoperative APACHE II score correlated with the increased TNF alpha concentration (r = 0.5, p < 0.001) and plasma lactate concentration with that of IL-6 (r = 0.7, p = 0.003). CONCLUSION: Perioperative TNF alpha and IL-6 concentrations correlated with the severity of intra-abdominal infection, so it is possible that patients who present with either septic shock or the sepsis syndrome may benefit from immunotherapy against TNF alpha.

Abdomen↗
PubMed1992

Combined sclerotherapy and operation for the treatment of bleeding oesophageal varices.

OBJECTIVE: To identify prognostic factors in a consecutive series of patients with bleeding oesophageal varices and develop an optimum regimen of treatment. DESIGN: Retrospective review. SETTING: I Department of Surgery, University Hospital, Vienna, Austria. PATIENTS: 301 consecutive patients with bleeding oesophageal varices. OUTCOME MEASURES: Median survival and survival at one year after sclerotherapy alone (n = 213), or sclerotherapy with portosystemic shunt (n = 54), Hassab's devascularisation (n = 29), or liver transplantation (n = 5). RESULTS: Prognosis was dependent on the severity of liver damage at the start of treatment. Median survival for Child's class A was 47 months, for Child's class B 54 months, and for Child's class C 2 months. The overall one year survival for patients in Child's class C was 33%, for sclerotherapy alone 28%, and for sclerotherapy and portosystemic shunt 42%, Hassab's devascularisation 50%, and liver transplantation 80%. CONCLUSION: Despite the small number of patients who underwent liver transplantation and their poor initial prognosis (Child's class C, n = 4; class B, n = 1) our results suggest that liver transplantation should be considered for the treatment of patients with end stage cirrhosis and bleeding varices.

Adolescent↗
PubMed1991

[Etiology and consequences of postoperative wound infection].

The incidence of postoperative wound infection ranges between 4.6% and 36% after gastrointestinal operations respectively. To evaluate the factors which influence the postoperative wound infection we prospectively analyzed our patients between 1/1989 and 1/1990. 444 patients from three general surgical units of our clinic entered this study. The overall wound infection rate was 6.3%. We classified the patients into 3 operative groups: Group I: subcutaneous operations; Group II: intraabdominal operations without opening the GI-tract; Group III: gastrointestinal operations. Wound infection rate in group I was 1.8%, in group II 7.3% and in group III 13.7%. The differences were highly significant. Both univariate (chi 2-test) as well as a multivariate (Cox-Model) analysis were done. We figured out that classification of patients (p = 0.000), operation time (p = 0.009), operating room (p = 0.000), intensive care unit (p = 0.026), long-term antibiotic prophylaxis (p = 0.001), subcutaneous haematoma (p = 0.000) and length of closed drainage time (p = 0.001) are of significant value. In the Cox model the classification of patients into 3 groups surpassed all the other factors. Postoperative hospital stay was lengthened in patients with wound infection significantly (p = 0.0025).

Austria↗
PubMed1991

[Results of transverse tracheal resection in post-intubation tracheal stenoses].

Tracheal problems in form of stenosis and malacia are a calculated risk of long-term tracheal intubation. Results with conservative treatment of such problems by bougienage, laser therapy, biopsy, cryotherapy, local steroids, tracheal stenting, and tracheostomy are not satisfactory in a higher percentage of cases. Resectional therapy of benign tracheal lesions has become an established technique, which combines excellent functional results with a low complication incidence. We have treated 40 patients of 17 to 76 years of age with postintubation tracheal lesions by cross resection of the affected segment. Of these patients 40% had received conservative therapeutical steps preoperatively. The mean resection length was 3.0 cm (1.5 to 6.5 cm). The perioperative morbidity was 7.8%, mortality was 2.5%. 85% of the patients operated between 1970 and 1989 were reached for a follow-up examination with x-ray, pulmonary function test and endoscopy. The patients subjective satisfaction with the operative result was good in 85%, minor in 12% and less in 3%. The objective investigations proved very good results in 90%. Our experience confirm the good results of other authors and recommend the resection treatment for cases of postintubation tracheal lesions.

Adolescent↗
PubMed1990

[The value of 2 distinct prognosis scores in patients with peritonitis. The Mannheim Peritonitis Index versus the Apache II score].

Seventy patients suffering from purulent peritonitis entered this study, 31 of them were taken in prospectively, to contrast two different prognostic scores, the Mannheim Peritonitis Index (MPI) vs. the Apache II (APS II). The MPI is shown as a prognostic index for peritonitis with high accuracy in individual prognosis. The simultaneous use of both scores, the MPI as well as the APS II, leads to a negligible improvement of prognostic accuracy. Moreover, sensitivity and specificity with the MPI are of higher accuracy than calculated with the APS II.

Adolescent↗
PubMed1989

The prognostic value of plasmaproteins in patients with abdominal sepsis.

In the course of the history of patients with severe peritonitis, opsonins, complements and other proteins of the plasma showed no significant difference between the data of the patients who later died or survived. We conclude that simple parameters like platelet count, creatinine and respiratory function are more sufficient.

Adult↗
PubMed1988

[Validation study of the Mannheim Peritonitis Index].

113 patients suffering from purulent peritonitis entered this retrospective study for evaluation of the prognostic value of the Mannheim Peritonitis-Index. There was no lethality below an index x = 21, between x = 21 and x = 29, it was 29% and lethality increased to 100% in patients with an index x greater than or equal to 30. Statistical validation showed that prognosis was correct in 93% for the index x = 27, with a sensitivity and specificity of also 93%. Between x = 21 and x = 29 prognosis of the MPI was correct in at least 65%. The MPI is shown as a prognostic index for peritonitis with high accuracy in individual prognosis, that could be easy routinely documented.

Adolescent↗
PubMedDate not supplied

Open approach in pancreatic and infected pancreatic necrosis: laparostomies and preplanned revisions.

One hundred and two patients with acute necrotizing pancreatitis were treated in accordance with a combined regimen of necrosectomy, open drainage by laparostomies, and repeated re-explorations. The severity of pancreatitis was assessed by the APACHE II score (median 15 on admission). Eighty-seven (85%) patients were classified as having infected pancreatic necrosis and only 15 (15%) as having pancreatic necrosis. Overall, 36 (35%) patients died, most of multiple organ failure. Survival was significantly impaired by bacterial contamination of pancreatic necrosis (p = 0.008), bacteremia (p = 0.0001) and infected bronchial secretions (p = 0.05). The mortality rate was reduced from 53% to 28% by changing the regimen of re-explorations from on demand to regular 48 hour intervals. Despite the fact that open packing was associated with a high frequency of gastrointestinal fistulas (30%), this concept seems to be a successful and recommendable approach in the therapy of pancreatic and infected pancreatic necrosis.

Acute Disease↗