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Biomedical subjects

G Kolb

Publications and source records attributed to G Kolb.

At least 19 recordsLinked to original sources

Comprehensive geriatric assessment in the elderly cancer patient.

The proportion of older cancer patients is increasing due to demographic and disease-specific reasons. However, this group of patients is severely underrepresented in research and clinical therapy. Limitation in physical and functional capacity with considerable interindividual heterogeneity remains one of the important problems in the treatment decision process. One approach to this problem is the use of a Comprehensive Geriatric Assessment (CGA) to describe and classify these deficits with high validity and reliability. The different domains of CGA are described with special respect to the instruments applied, as CGA has also a key role in the decision process.

Activities of Daily Living↗

[Therapy of elderly patients with colorectal carcinoma].

Treating elderly patients with colorectal cancer is a challenging task for which many aspects have to be taken into account. Almost 70% of patients with colorectal cancer are 65 years or older and the number of elderly patients is expected to increase. As elderly patients frequently exhibit adverse physical or socio-economic conditions, a thorough geriatric assessment of the patient's suitability for therapy is essential before making a decision. The first line treatment for colorectal cancer is surgery. Complete resection of the tumor should also be attempted in elderly patients, as there are little differences in cancer--specific survival in selected elderly patients compared to younger patients. Surgery with palliative intention can be attempted for symptom control or to prevent later local complications caused by the primary tumor. At present, adjuvant 5-FU based chemotherapy (in colon cancer) and adjuvant radio-chemotherapy (in rectal cancer) in the elderly is recommended for locally advanced or node positive tumor after tumor resection, since the benefit seems to be comparable to that achieved in younger patients. There is also enough data to support the use of 5-FU based chemotherapy in elderly patients in the palliative setting. New drugs have recently been added to the armentarium for the treatment of metastatic colorectal cancer. However, there is as yet not sufficient data to guide the use of these new drugs (such as oxaliplatin or irinotecan) in elderly patients. However, first clinical studies seem to indicate a comparable efficacy and toxicity in elderly patients to that observed in younger patients. Further clinical trials of chemotherapy in elderly patients with colorectal cancer are necessary to gain information about treatment recommendations. It is the aim of this manuscript to summarize the current knowledge about the management of colorectal cancer in elderly patients.

Aged↗

Use of hematopoietic growth factors in elderly patients receiving cytotoxic chemotherapy.

Myelosuppression is a common side effect in elderly patients undergoing chemotherapy. Neutropenia and anemia cause considerable morbidity, may increase mortality, and can result in a worse outcome of treatment in elderly patients compared to younger patients with comparable type and stage of disease. The availability and proven efficacy of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) have had a considerable impact on supportive care in cancer patients: Several randomized trials have demonstrated a reduction of neutropenia and the frequency of severe infections in elderly patients treated with G-CSF following myelotoxic chemotherapy compared with patients without growth factor support. Both for G-CSF and for recombinant human erythropoietin (rHu-EPO) several studies have demonstrated the safety and effectiveness of these molecules in elderly patients with regard to increasing hemoglobin concentrations, improving quality of life (rHu-EPO), and neutrophil recovery. Although a positive effect of the use of growth factors on overall survival in elderly cancer patients is not yet proven, a reduction of chemotherapy-induced side effects could clearly be shown. The National Comprehensive Cancer Network (NCCN) of cancer centers has recommended that all patients aged 70 years and older treated with CHOP or cytotoxic chemotherapy of comparable intensity should receive prophylactic G-CSF administration, and that the hemoglobin concentration be maintained at >or=12 g/dl in elderly patients undergoing chemotherapy.

Aged↗

Driving in vitro selection of anti-HIV-1 TAR aptamers by magnesium concentration and temperature.

In vitro selection with either DNA or RNA libraries was performed against the TAR RNA element of HIV-1. The role of the selection conditions on the outcome of the selection was evaluated by varying the magnesium concentration and the temperature. The selection stringency was demonstrated to determine i) the affinity of the best identified aptamers for the TAR target, and ii) the type of interaction between the two partners. Selections performed with a DNA library under low (4 degrees C, 10 mM magnesium) and high stringency (23 degrees C, 3 mM magnesium) led to the emergence of "kissing aptamers"; but even if the motif interacting directly with the TAR loop were identical in the two kinds of aptamers, the consensus was extended from eight to thirteen nucleotides when the Mg(2+) concentration was decreased from 10 to 3 mM. Similar kissing aptamers were selected at 23 degrees C and 37 degrees C starting with two different RNA libraries under identical ionic conditions. In addition, selection performed at 37 degrees C yielded a significant proportion of antisense sequences. Only antisense RNAs complementary to the TAR loop competitively inhibited the association of a Tat peptide with TAR.

Base Sequence↗

[Chemotherapy of colorectal cancer--which therapy is justified for elderly patients?].

Treating elderly patients with colorectal cancer is a challenging task for which many aspects have to be taken into account. 70% of patients with colorectal cancer are 65 years or older and the number of elderly patients is expected to increase. As elderly patients frequently exhibit adverse physical or socio-economic conditions, a thorough geriatric assessment of the patient's suitability for therapy is essential before making a decision. At present, adjuvant 5-FU based chemotherapy (in colon cancer) and adjuvant radio-chemotherapy (in rectal cancer) in the elderly is recommended for locally advanced or node positive tumor after tumor resection, since the benefit may be comparable to that achieved in younger patients. There is enough data to support the use of 5-FU based chemotherapy in elderly patients in the palliative setting. New substances have recently been added to the armentarium for metastatic colorectal cancer. However, there is as yet not sufficient data to guide the use of these new drugs (such as oxaliplatin or irinotecan) in elderly patients. However, first clinical studies seem to indicate a comparable efficacy and toxicity in elderly patients to that observed in younger patients. Further clinical trials of chemotherapy in elderly patients with colorectal cancer are necessary to gain information about treatment recommendations.

Aged↗

The pre-, peri-, and postsurgical activation of coagulation and the thromboembolic risk for different risk groups.

Patients after surgery stand at high risk of developing thromboembolic complications. Nevertheless, there is at present no universal and valid guideline on the duration of heparin prophylaxis. This study aims to assess the thromboembolic risk after the different surgical treatments for different risk groups, based on the activation of the plasmatic coagulation and fibrinolysis system. This is measured by estimating the levels of the fibrin monomers (FM) and fibrin-D-dimers (FD) in plasma during the pre-, peri-, and postsurgical periods in patients from the different clinical risk categories (i. e., posttraumatic or elective hip replacement and osteosynthesis and abdominal surgery: conventional or minimal invasive in malignant and non malignant diseases). During an observation period of 14 days the FM and FD levels were found to be significantly elevated in patients from all risk groups. Underlying malignant diseases lead to an elevation of the procoagulatory risk, whereas age itself does not. Patients who underwent hip surgery seemed to be especially at risk. Even after 14 days or at the date of discharge the FM and FD levels were elevated to maximum showing sustained precoagulatory conditions and increased thromboembolic risk. For these patients the long-term prophylaxis, lasting possibly longer than the average hospitalization period, seems evident. Clinical trials to prove this hypothesis are nevertheless urgently recommended. A corresponding clinical trial that compares long-term against standard heparinization was therefore initiated and is now in progress.

Adult↗

Biocompatibility differences with respect to the dialyzer sterilization method.

The impact of the method of sterilization (steam vs. ethylene oxide, ETO) on indices of biocompatibility is investigated using polysulfone membranes. Eight patients were treated with a random choice of the high-flux membranes F60S (steam) and F60 (ETO) and the low-flux membrane F6 (ETO). Blood samples were taken prior to and 5, 15, 30, 60, and 180 min after the start of hemodialysis. White blood cell count, platelet count, and plasma concentrations of polymorphonuclear neutrophil elastase, complements C3a and C5a, and beta2-microglobulin were determined. The dialysis procedure was associated with a significant decrease in white blood cell count and beta2-microglobulin level and a significant increase in polymorphonuclear neutrophil elastase and complement C3a and C5a levels. However, the steam-sterilized F60S membrane had a significantly lower impact on the biocompatibility indices than the ETO-sterilized F60 and F6 membranes (p < 0.05 or p < 0.001 for the individual markers). We conclude that using steam instead of ETO for sterilization may improve the biocompatibility of membranes.

Adult↗

[Clinical value of the CA 19-9 tumor marker with special reference to the Lewis phenotype].

BACKGROUND: Because of structure and biosynthesis of CA 19-9, it was postulated that patients with the Lewis phenotype Le(a-b-) are not able to synthesize CA 19-9. But some patients with Le(a-b-) on red blood cells showed elevated levels of this tumor marker. PATIENTS AND METHOD: In 164 patients suffering from benign or malignant diseases both CA 19-9 and the Lewis phenotype were determined in sera. In addition in 51 patients red blood cells were tested for Lewis substances. RESULTS: The frequencies of the different Lewis phenotypes on red blood cells were compared with the results found in sera. The prevalence of the phenotype Le(a-b-) on erythrocytes was significantly higher than in sera. In 51 patients both determinations were performed. These results were compared additionally. The phenotype Le(a-b-) found on red blood cells agreed with the results found in sera only in 30% of the cases. A loss of Lewis substances on erythrocytes could be seen both in malignant and benign diseases. Only in patients with Lewis substances found in sera elevated levels of CA 19-9 could be seen. CONCLUSION: Considering only the Lewis phenotype in sera, it could be confirmed that patients with the genotype Le(a-b-)are not able to express elevated concentrations of CA 19-9.

Aged↗

[Metachromatic leukodystrophy simulating schizophrenia-like psychosis].

A case of late onset metachromatic leukodystrophy with a clinical picture of paranoid hallucinatory psychosis and severe dyskinesia is described. The problem of diagnostic recognition is discussed. In the case, diagnostic procedures were initiated after atypical clinical course, and established on the basis of MRI and specific biochemical tests.

Adult↗

Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a county of Hesse, Germany.

The incidence of acute and chronic myelogenous leukemia has been compared for the two neighbouring regions of Marburg and Giessen in Hesse (Germany). The investigation was based on the incident cases of the years 1983-1989 which have been diagnosed in the hematological departments of the universities of the two regions. The epidemiological evaluation of the data has been carried out in terms of a historical follow-up study, and shows an increased relative risk for the region around Marburg with a particular elevation for one community within this region. Potential determinants are discussed and focus on trinitrotoluene (TNT) and decomposition products which are known to contaminate the soil of this community, in some places severely, due to insufficient removal of remnants of the TNT production in large underground plants during World War II.

Adult↗

Granulocyte-monocyte colony-stimulating factor levels during hemodialysis-induced leukopenia.

Hemodialysis (HD), especially with cellulosic membranes, leads regularly to a transient but marked drop of peripheral neutrophils. Such neutropenia during the initial 10-30 min of HD is followed by a reincrease in granulocyte count up to a mild leukocytosis. Although this phenomenon accounts for the best documented side effect of HD, little is known about the underlying regulatory mechanisms. Therefore in this study the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured during HD. Previous investigations have demonstrated that GM-CSF plays the central role in controlling the homeoiostasis of leukocytes by up- and downregulation of proliferation and efflux of cells out of the maturation compartment within the bone marrow. Three patients with chronic renal failure underwent HD with cuprophane membranes. In all cases a significant drop of peripheral granulocytes occurred, but GM-CSF levels remained unchanged and were found in the normal range during the whole period of the treatment. It is therefore concluded that GM-CSF may not be significantly involved in the regulation of peripheral leukocytes during HD.

Cellulose↗

Protein S degradation in vitro by neutrophil elastase.

Human protein S is degraded by neutrophil elastase. The characteristics of cleavage are compared in a purified protein S preparation, a concentrate of vitamin K-dependent proteins (PPSB) and in normal plasma as well as in alpha-proteinase inhibitor (alpha PI)- deficient plasma. Elastase incubation of purified human protein S (molar enzyme-to-substrate-ratio 1:5500-1:55) reduces the molar mass of the native protein S (81-83 kDa) to about 79 kDa by cleavage of a small peptide. Incubation with very high elastase concentrations (molar enzyme-to-substrate-ratio 1:5.5) completely degrades protein S into small fragments. The elastase incubated protein S has a higher isoelectric point than the native form (Ip 5.9 vs. 5.3). Protein S in a PPSB coagulation factor concentrate is degraded in the same way as isolated protein S. By immunoblotting also smaller split products of molar masses between 34 and 70 kDa are demonstrated. In normal plasma protein S is not degraded by elastase concentrations up to 14 mumol l-1. In plasma of a patient with alpha 1-proteinase inhibitor deficiency protein S can be degraded by elastase. The native 82 kDa protein is degraded to a 72 kDa protein. PEG precipitation of the protein S- C4b- binding protein-complex shows that elastase predominantly splits the free protein S.

Blood Coagulation Factors↗

Felty's syndrome: favorable response to granulocyte-macrophage colony-stimulating factor in the acute phase.

We report a case of Felty's syndrome in which infectious complications due to severe neutropenia could be overcome by short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 7 micrograms/kg/day s.c.). Leukocyte counts rose from 1,050/mm3 at presentation to 4,470/mm3 after 15 days of treatment. A flare-up of arthritis was not noted. Defects in granulocyte function and clinical improvement prior to leukocyte rise suggest that the beneficial effect of GM-CSF is mainly due to an improvement of granulocyte function.

Acute Disease↗