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Biomedical subjects

D Nitsche

Publications and source records attributed to D Nitsche.

17 recordsLinked to original sources

Biochemical modulation of 5-fluorouracil by leucovorin with or without interferon-alpha-2c in patients with advanced colorectal cancer: final results of a randomised phase III study.

5-Fluorouracil (5-FU) remains the mainstay of treatment for advanced colorectal carcinoma, although response rates are generally less than 20%. Improved therapeutic efficacy has been reported using biochemical modulation of 5-FU by leucovorin (LV) or interferon alpha (IFN), the combination of 5-FU/LV frequently considered as standard therapy in metastatic colorectal cancer. In an attempt to enhance the cytotoxicity of 5-FU, a prospective randomised trial was initiated to compare 5-FU/LV with 5-FU/LV plus IFN. Patients were randomised to receive either LV, 100 mg/m2 intravenously (i.v.), followed by 5-FU, 500 mg/m2 as a 1-h i.v. infusion, daily for 4 days, followed by weekly infusions until week 8, or the same regimen of 5-FU/LV plus IFN-alpha-2c, 30 micrograms subcutaneously (s.c.), three times weekly. Cycles were repeated after a 2-week rest period. Among 269 enrolled patients, 219 were available for response and 243 for toxicity. An objective tumour response was observed in 38 of 107 (36%) and 28 of 112 (25%) patients in the treatment arms with and without IFN, respectively (difference not significant). There was no significant difference between the two groups in response duration (median 8.4 versus 12.1 months), time to treatment failure (median 6.5 versus 4.9 months), or overall survival (median 10.0 versus 12.6 months). However, patients in the IFN arm experienced significantly more haematological and gastrointestinal toxicity and more frequent alopecia. In conclusion, the addition of IFN to 5-FU/LV in the schedules and doses used in the study did not provide any clinical benefit over 5-FU/LV alone and cannot be recommended for routine use in the treatment of advanced colorectal cancer.

Adult↗

Impact of different classes antimicrobial agents on plasma endotoxin activity.

OBJECTIVE: To investigate the influence of different classes and doses of antibiotics on endotoxin release in gram-negative infection in a rat model of intra- abdominal infection. DESIGN: Immediately after intraperitoneal inoculation of Escherichia coli (5 x 10(7) colony-forming units/kg), anesthetized Wistar rats were treated with a single intravenous dose of an antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxacin (3 mg/kg or 6 mg/kg), imipenem (7 mg/kg or 14 mg/kg), or gentamicin (5 mg/kg). An untreated control group received 0.9% sodium chloride instead of antibiotic. Plasma endotoxin activity, blood bacteria count, and mean arterial pressure were monitored at 60-minute intervals for 5 hours. At the end of the experiment, lavage was performed to determine the bacteria count in the peritoneal cavity. RESULTS: In the untreated group, the blood bacteria count increased rapidly. Five hours after therapy, the plasma endotoxin activity in the cefotaxime group was higher by a factor of 3.6 than in the untreated group. Compared with the cefotaxime group, endotoxin activity was approximately 26% lower in the ciprofloxacin (3 mg/kg) group, 35% lower in the imipenem groups, and 38% lower in the gentamicin group. The lowest endotoxin levels were in the high-dose ciprofloxacin group. Bacteria counts in the peritoneal cavity were lowest in the gentamicin and high-dose ciprofloxacin groups. Except in the high-dose ciprofloxacin group, the endotoxin increase in the therapy groups was associated with a significant (P < .05) decrease in mean arterial pressure. CONCLUSIONS: In the early phase of therapy, antibiotic-induced endotoxin release is influenced by the mode of action of the agent class. This is not the sole influence in every class. With quinolones, this effect is also influenced considerably by dosage, ie, by pharmacodynamics.

Animals↗

Influence of immunoglobulin and interleukin 2 on the translocation of microorganisms from gut into blood.

The aim of this study was to influence the translocation of microorganisms and endotoxin from the gut of septic rats by the intravenous (i.v.) administration of immunoglobulin and interleukin 2. Acute infection was induced in all animals by an intraperitoneal bacterial challenge of 2 x 10(6) microorganisms (Ps. aeruginosa, E. coli, Kleb. pneumoniae). Immediately after the bacterial challenge control animals were given albumin i.v. whereas the experimental groups were given immunoglobulin or interleukin 2. A significant reduction of bacteria in the plasma of rats was observed in immunoglobulin treated animals (10,000 CFU/ml vs 450 CFU/ml). This was accompanied by an increase of plasma endotoxin of nearly 100% within the first 2 h. Interleukin 2 essentially did not change the bacterial count in comparison with albumin-treated control animals but reduced the endotoxin level in plasma up to tenfold. It is concluded that both immunoglobulins and interleukin 2 are involved in severe infections. Whereas immunoglobulins reduce bacterial translocation, interleukin 2 stimulates the elimination of endotoxin.

Animals↗

[Functional pathomechanisms of anal fissure].

In a prospective consecutive study of 40 patients with anal fissure we analysed the anal sphincter function at rest and rectal distension. Healthy persons with comparable age and sex distribution were controls. The anal pressures were registered with thin water perfused catheters (2 ml/min). Our patients with anal fissure showed significant elevation of anal pressures at rest along the whole length of anal canal. During rectal distension only the distal part of anal sphincter (up to a level of 2 cm from the anocutaneous line) showed a spasm with reduced relaxation. Our results are useful for operative therapy, since lateral internal sphincterotomy corresponds very well to functional pathomechanism of anal fissure.

Adult↗

[Blast crisis in chronic myeloid leukemia. Results with vindesine and prednisolone].

Nine patients with blast crises of chronic myeloid leukaemia were treated with a combination of vindesine and prednisolone. Vindesine, 2 mg/m2, was administered intravenously on two successive days each week and prednisolone, 60 mg/m2, orally once daily. Blast crises were divided into myeloblastic and lymphoblastic ones using cytochemical parameters as well as detection of terminal deoxynucleotidyl transferase. Complete remission was achieved in four patients, partial remission in one patient; in four patients treatment was unsuccessful. According to cytochemical findings, a therapeutic success was obtained in three of four patients with lymphoblastic and two of four patients with myeloblastic crises whereas no response to the treatment was seen in one patient with an undifferentiated type. Side effects of the therapy were frequent, but of only low degree and never led to interruption of treatment. On the basis of these results and from experience reported in the literature, the combination of vindesine and prednisolone can be recommended as the therapy of choice in blast crises of chronic myeloid leukaemia.

Adult↗

[Pathogenesis and morphology of anal fistulas].

In a prospective consecutive study in 80 patients with anal fistulous disease we found characteristics in the morphology of the fistulous tracks, which correspond to the structure of anal glands. The theory of a cryptoglandular infection as the cause of anal fistulous disease seems to be realistic for this reason. The chronic fissure in ano represents likewise a pathogenetic factor in the genesis of anal fistula, especially in the posterior part of the anal canal. In this region we found trans- and suprasphincteric tracks with abscesses in the fossa ischiorectalis. Anal fistulas as a consequence of specific intestinal infections could be found only in 6%, whereas unspecific fistulas with inter- and transsphincteric tracks amounted to 90%.

Abscess↗

[Pre- and postoperative fibronectin concentrations in the serum of patients with severe peritonitis in comparison with postoperative courses without complications].

Fibronectin in serum was determined in surgical patients with and without severe peritonitis. It could be observed that the infection induced an intense reduction of fibronectin, which could not be found in patients without postoperative complications. Extremely low values were detected in patients not surviving the infection. They remain unchanged during the observation time. Patients with severe infections, which survived, did show higher fibronectin values which significantly increased during the observation time. Together with other parameters and clinical symptoms fibronectin could be used to indicate the prognosis of severe infections.

Fibronectins↗

[Results of cytostatic polychemotherapy in non-Hodgkin lymphomas].

109 patients with advanced stage non-Hodgkin lymphomas were treated with cytostatic chemotherapy. 91 of these patients were classified according to the Kiel classification as having lymphomas of low-grade malignancy, whilst the remaining 18 had lymphomas of high-grade malignancy. The primary treatment in low-grade malignant lymphomas was a combination of chlorambucil and prednisone: in case of progression or therapeutic failure more aggressive schedules (COP, C-MOPP, HOP, CHOP, BACOP) were used. Patients with high-grade malignant lymphomas were treated in the first instance according to these aggressive schedules. Although no complete remissions were achieved, 25 out of the 47 patients with CLL responded with a partial remission to chlorambucil/prednisone, whilst 12 out of 19 non-responders to this schedule reacted favourably to COP. The results in 10 patients with immunocytic lymphomas were of a similar order. Better results were achieved in patients with germinal centre tumours: 9 out of the 11 patients with centrocytic lymphomas and all 20 patients with centrocytic-centroblastic tumours responded with a complete or partial remission. Of 18 patients with high-grade malignant lymphomas, 5 responded with a complete remission, 8 with a partial remission.

Antineoplastic Combined Chemotherapy Protocols↗

[Contents of glycogen, glycolytic activity and contents of metabolites in the atrioventricular system of bovine hearts (author's transl)].

In the atrioventricular system (AVS) consisting of the compact node, the penetrating bundle and the branching bundles of about 250 bovine hearts there were made several studies: 1. In quickly removed and fixed specimens (distal AV-node, penetrating bundle) determination of a metabolic state with respect to glycogen, glucose, lactate, ATP, ADP, AMP, creatinephosphate, total creatine, gluc-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, dihydroxyacetonphosphate and pyruvate. 2. Determination of glycogen contents and glygolytic activity in AVS and its parts for ischemic times up to three hours. 3. The determination of metabolic contents in samples of connective tissue in atrium and ventricle of bovine hearts. The AV-nodes are poor in glycogen comparable with glycogen content of central nervous system and other ganglia. Penetrating bundles of Hiss and branching bundle belong after liver to the glycogen richest parenchyma of animal tissues. Even after ischemia of 3 h only a part of glycogen was recovered as lactate. The greater part of glycogen must be considered as a structural element of Hiss bundle and branching bundles of the ventricles.

Adenosine Diphosphate↗

[Postoperative changes in immunoglobulin-concentrations after splenectomy. A prospective survey series (author's transl)].

The three immunoglobulin classes A, G and M were quantitatively determined through immune diffusion preoperatively as well as in the first 60 days in 31 patients after splenectomy and the results were statistically evaluated. In comparison with the initial preoperative values, a temporary, significant elevation of the serum concentration of the IgA and IgG was found, whereby the IgA concentration on the 60th postoperative day corresponded already to the preoperative initial values, whilst the IgG were at this time still significantly elevated. There was a beginning significant decrease in serum concentration of the IgM between the 15th and 20th postoperative day, which was very pronounced on the 60th day. This determination coincides with the half-life time of the IgM and can be regarded as an indication for a localisation of the IgM producing cells in the spleen.

Female↗