Acute myeloid leukemia with near-triploid karyotype and extramedullary involvement of mediastinum.
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Adult↗
Biomedical subjects
U Mey
Publications and source records attributed to U Mey.
Primary extragonadal germ cell tumour: unusual localization of a c-kit mutated retroperitoneal seminoma in the gastric wall.
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Adult↗
Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine.
Serum carbohydrate antigen 19-9 (CA 19-9) has been identified as a useful tumour marker for diagnosis of exocrine pancreatic carcinoma, but its value for evaluating the response to chemotherapy with gemcitabine is not clear. Tumour regression in pancreatic carcinoma is hard to determine due to massive desmoplastic tissue. Furthermore, objective tumour response does not automatically transcribe into better survival. Therefore, clinical benefit response, a composed parameter consisting of factors like performance status, pain, and body weight was integrated in evaluating tumour response. The aim of this prospective study was to evaluate the usefulness of serial CA 19-9 measurements as a biochemical response marker and an outcome prognostic parameter in patients with advanced pancreatic cancer receiving gemcitabine treatment. A total of 46 consecutive patients (median age 66 years) suffering from histologically proven locally advanced or metastatic adenocarcinoma of the exocrine pancreas were analysed. Gemcitabine was applied for a median of 23 courses (range 6-76). Two patients achieved an objective complete remission, five an objective partial remission (overall response, OR=15.2%), while objective stable disease was documented in 19 and objective progressive disease in 20 patients. Patients with a decrease of >20% of the baseline CA 19-9 level after 8 weeks of chemotherapy had a significantly better median survival than patients with a rise or a decline <20%. The response of CA 19-9 >20% during chemotherapy was the only independent predictor of survival in a multivariate analyses. In contrast, neither objective tumour response nor clinical benefit response showed this level of significance. In conclusion, kinetics of CA19-9 serum concentration serves as an early indicator of response to gemcitabine chemotherapy in advanced pancreatic cancer.
Adenocarcinoma↗
Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison.
GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.
Adolescent↗
Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial.
Docetaxel has consistently demonstrated its high activity as an antineoplastic agent in the treatment of metastatic breast cancer. However, 90% of patients receiving the recommended dose of 100 mg/m2 every 3 weeks will develop grade 3 or 4 neutropenia. Recent data suggest that the safety profile of a weekly docetaxel regimen compared favorably with the standard 3-week schedule. Thus, we initiated a phase II study to assess the efficacy and toxicity of weekly docetaxel in pretreated patients with metastatic breast cancer. Twenty patients with advanced, anthra-cycline-refractory breast cancer were included in this phase II trial. Docetaxel was administered at a starting dose of 40 mg/m2, repeated once a week for 3 consecutive weeks followed by a 1-week rest period (1 cycle). Patients were evaluated for tumor response every 8 weeks (after every other cycle). Therapy was continued for a maximum of six courses in patients showing tumor response or stable disease. Twenty patients received a total of 204 weekly infusions of docetaxel. The mean number of treatments was 10.2 (range 1-18). Eighteen patients were assessable for response. Five patients achieved a partial response and six patients showed either stable disease or a minor response. Seven patients had disease progression. The median survival was 7.8 months. Grade 3/4 leukopenia occurred in two patients. No other grade 3 or 4 hematologic toxicities were observed. The following grade 3/4 non-hematologic toxicities were seen: nausea/vomiting (one patient), infection (one patient), mucositis (two patients) and diarrhea (one patient). Three patients withdrew from the study due to dose-limiting toxicities (one due to severe neutropenia and two due to mucositis). We conclude that administration of docetaxel at a dose of 40 mg/m2 was effective and well tolerated even in heavily pretreated patients with metastatic breast cancer. This regimen is associated with only mild myelosuppression.
Adult↗
Evaluation of an ultrasound-guided technique for central venous access via the internal jugular vein in 493 patients.
Ultrasound guidance for percutaneous puncture of the internal jugular vein provides many advantages over the classic landmark-guided technique, particularly in complicated cases (e.g. thrombocytopenia, obesity, dyspnea). The present prospective investigation involved analysis of 493 punctures and provides patient- and operator-dependent variables with respect to the impact on puncture success and the complication rate. These 493 punctures of the internal jugular vein were performed using identical puncturing equipment and a standardized two-operator catheterization technique and were prospectively recorded on the hematology-oncology ward of a university hospital. Alongside success rates, the frequency and nature of complications, patient-inherent risk variables (obesity, thrombocytopenia, patient cooperation, vein diameter, etc.) and the individual experience of the physician performing the puncture and ultrasound were analyzed with respect to possible impact on success and complication rate. Internal jugular vein cannulation was successful in 94.5% of all patients. Catheter placement was successful at the first attempt in 87.6% of cases. Arterial fail punctures occurred in 1.4% of the patients and local hematoma in a further 4.3%. Among the patient-dependent variables, only poor patient compliance and a maximum vein diameter smaller than 7 mm showed a negative influence on the success rate. The experience of the physician carrying out the puncture influenced neither the success rate nor the complication rate. In contrast, both failure and complication rates were significantly lower when the physician guiding the sonographic probe was familiar with the method. Ultrasound-guided cannulation of the internal jugular vein provides safe central venous access with high success rates and low complication rates. Difficulties due to patient-inherent risk factors (e.g. thrombocytopenia, obesity, dyspnea) can be managed well using ultrasonographic guidance. The success rate achieved and the frequency of complications are decisively influenced not by the experience of the physician performing the puncture, but by the experience of the physician acting as sonographer.
Adult↗
[Palliative therapy of inoperable cholangiocarcinoma].
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Antineoplastic Agents↗
Low frequency of enteric infections by Salmonella, Shigella, Yersinia and Campylobacter in patients with acute leukemia.
BACKGROUND: Several authors found that isolation of Salmonella, Shigella, Yersinia and Campylobacter spp. (SSYC) from stool cultures after the 3rd day of hospitalization is a rare event. The significance of enteric infections caused by these pathogens has not been systematically investigated in severely immunosuppressed patients with acute leukemia. PATIENTS AND METHODS: We screened all patients treated on the leukemia ward of a university medical center. A total of 1,185 stool cultures from 371 episodes of diarrhea, mostly following myelosuppressive chemotherapy, were examined for the complete range of classic bacterial enteric pathogens (i.e. SSYC). RESULTS: Only three (0.25%) cultures from one patient were positive for Salmonella enteritidis. This patient suffered from cholangitis. S. enteritidis could also be detected by liver biopsy. Other infections by classic enteric pathogens were not observed. CONCLUSION: Symptomatic infections by classic bacterial enteric pathogens in hospitalized patients with acute leukemia are very rare. Stool cultures for these pathogens cannot be recommended as a routine test in uncomplicated diarrhea occurring after the 3rd hospital day.
Acute Disease↗
Acute transient encephalopathy after paclitaxel infusion: report of three cases.
Paclitaxel (Taxol) is a diterpene plant product and antineoplastic agent that promotes the assembly of microtubules as well as stabilizing their formation by preventing depolymerization. Myelosuppression was found to be dose-limiting, but peripheral neurotoxicity is also a well known side-effect. Central nervous system toxicity is rare, probably because paclitaxel does not cross the blood-brain barrier. We observed three patients who presented with acute encephalopathy within 6 h after infusion of paclitaxel at normal doses. All patients had received prior whole brain irradiation (WBI) and one patient had prior brain metastasectomy. Computer tomography and magnetic resonance imaging showed no evidence of cerebral metastases. An effect from other organ toxicities was excluded in all patients. All recovered spontaneously within 4-6 h. From this we can conclude that paclitaxel can cause severe acute transient encephalopathy, which may occur more frequently after prior WBI and/or surgery due to alteration of small vessel function.
Aged↗
[Therapy-refractory thrombocytopenia in chronic hepatitis C].
HISTORY AND CLINICAL FINDINGS: A 74-year-old man known to be suffering from a chronic hepatitis C infection was hospitalized because of intestinal hemorrhage, multiple petechiae and suggillations. The patient had received oral anticoagulant medication after replacement of the mitral valve. The intake of oral vitamin K antagonist had been discontinued eight days before admission. EXAMINATION FINDINGS: On admission, the platelet count was 3 G/l, the Quick's test 72%. Colonoscopy revealed diffuse mucosal bleeding in the proximal colon. Bone marrow examination showed moderate hyperplasia of erythropoiesis, as well as a marked increase in megakaryocytes. DIAGNOSIS, THERAPY AND COURSE: The diagnosis was hepatitis C-associated idiopathic thrombocytopenic purpura. The administration of both immunoglobulins and prednisone failed to increase platelets sufficiently. There was also no improvement after administration of Danazol. However, six days after a single application of cyclophosphamide (2,000 mg on day 1), a continuous increase of platelets to 100 G/l was obtained, a level which has remained stable for the last 18 months. CONCLUSION: The differential diagnosis of a hepatitis C-associated autoimmune thrombocytopenia must be considered in patients with chronic hepatitis C infection and severe thrombocytopenia. In cases of refractory disease, treatment with cyclophosphamide may be successful. This is particularly appropriate if, in the case of an insufficient increase in thrombocytes following administration of immunoglobulins, the success of a splenectomy is improbable, or when a splenectomy must be excluded because of relative or absolute contraindications.
Aged↗
Comparative N-glucuronidation kinetics of ketotifen and amitriptyline by expressed human UDP-glucuronosyltransferases and liver microsomes.
Like other basic amphiphilic drugs, the (S)-enantiomer of the antiallergic drug ketotifen exhibited biphasic kinetics when it was converted to two isomeric quaternary ammonium-linked glucuronides in human liver microsomes. For (R)-ketotifen this applied when incubations were carried out in the absence of a detergent. Two UDP-glucuronosyltransferases (UGTs) present in human liver, UGT1A4 and UGT1A3, were previously shown to catalyze tertiary amine N-glucuronidation when expressed in HK293 cells. Therefore, the conjugation kinetics of (R)- and (S)-ketotifen were investigated with the two expressed proteins. When homogenates of HK293 cells expressing UGT1A4 were incubated without detergent, N-glucuronidation kinetics were monophasic with K(M) values of 59 +/- 5 microM for (R)- and 86 +/- 26 microM for (S)-ketotifen. In experiments with membranes containing expressed UGT1A3, somewhat higher K(M) values were obtained. These values correspond to the high rather than to the low K(M) components of ketotifen glucuronidation in liver microsomes, the latter exhibiting K(M) values around 2 and 1 microM, respectively, with (R)- and (S)-ketotifen. With amitriptyline as the substrate, N-glucuronidation kinetics in the absence of detergent were biphasic in human liver microsomes and monophasic with a high K(M) value in cell homogenates containing UGT1A4. The results suggest that UGT1A4 and UGT1A3 catalyze high-K(M) N-glucuronidation of tertiary amine drugs, whereas the low-K(M) reaction requires either an alternative enzyme or a special conformation of UGT1A4 or UGT1A3 that can be attained in liver microsomes, but not in HK293 cell membranes.
Amitriptyline↗
Conjugation of the enantiomers of ketotifen to four isomeric quaternary ammonium glucuronides in humans in vivo and in liver microsomes.
The antiallergic drug ketotifen is chiral due to a nonplanar seven-membered ring containing a keto group. Earlier studies have revealed glucuronidation at the tertiary amino group as a major metabolic pathway in humans. Chemical synthesis of glucuronides from racemic ketotifen now led to four isomers separable by HPLC of which two each could be ascribed to (R)-(+)- and (S)-(-)-ketotifen by synthesis from the enantiomers. According to (1)H NMR analysis of the (S)-ketotifen N-glucuronides, the conformation of the piperidylidene ring differs between the two isomers. Enzymatic hydrolysis with Escherichia coli beta-glucuronidase proceeded at a lower rate with the slower eluting (S)-ketotifen glucuronide than with the three other isomers. On incubation of the ketotifen enantiomers (0.5-200 microM) with human liver microsomes in the presence of UDP-glucuronic acid and Triton X-100, the N-glucuronides of (R)-ketotifen were produced with an apparent K(M) 15 microM and V(max) 470 pmol/min/mg protein. The two (S)-ketotifen glucuronides were formed by two-enzyme kinetics with K(M1) 1.3 microM and K(M2) 92 microM and V(max) values of 60 and 440 pmol/min/mg protein. After ingestion of 1 mg of racemic ketotifen, 10 healthy subjects excreted in urine 17 +/- 5% of the dose in the form of N-glucuronides. The (R)-ketotifen glucuronide isomers contributed one-sixth only, whereas the remainder consisted primarily of the (S)-ketotifen glucuronide isomer, which eluted last. Differential hydrolysis or membrane transport may be responsible for the discrepancy between N-glucuronide isomer ratios in vitro and in vivo.
Anti-Allergic Agents↗
[Viewpoints on the problem of subspecialization in internal medicine].
There is no doubt that the specialisations which were performed during the last two to three decades in the field of internal medicine decisively furthered the scientific progress also in this subject. From the more and more detailed insights into the pathological process connected with this and the opening of more and more far-reaching therapeutic possibilities, however, resulted also with regard to the patients' care an increasingly organ-related medicine, which lost sight of the patient as a subject and personality. It has been omitted that the purely natural-scientifically orientated way of consideration is only one side of medical activity and that for recognition of all aspects of the homo patients internal medicine has to make use also of comprehensions and experiences of arts and social sciences. The synthesis of the two roots, connected with a subspecialization restricted to the necessary measure and its integration into a patient-orientated total concept of internal medicine should be able to reasonably coordinate scientifically explored facts, technical achievements, ethical things and things expected by the patient.
Germany, East↗
[Immunotherapy of cancer--status and perspectives].
Already since more than 80 years in medicine a cancer control by means of immunological methods has been tried again and again. In the last decennium above all the possibilities of the immunostimulation and the immunopotentiation as therapeutical principle were investigated. But neither the influence on the macrophages and the NK-cells perhaps by BCG, MDP, interferons or similar things nor the application of a tumour vaccine, e.g. blasts stimulated with neuraminidase, nor the T-lymphocyte stimulation, e.g. by thymus factors or levamisol, nor the activation of the specific tumour defence possibly by interleukins or clonic killer-cells brought a decisive breaking forth. Only in some certain malignant diseases, such as in virus-induced leukaemias or non-Hodgkin lymphomas of the B-cell series, by means of interferon and monoclonal anti-idiotype-antibodies, respectively, principal possibilities of an immunotherapy could be revealed. The question arises, whether the concept of an immunological tumour control underlying the previous therapeutic efforts really proves right or whether or not the recent knowledge about the principle of the oncogenes should give rise to a change of therapeutic thoughts.
Adjuvants, Immunologic↗
Low-dose Ara-C treatment in elderly patients with acute myeloblastic leukemia.
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Aged↗
[Medical Society of Magdeburg in 1848--a medical history reflection].
The Medical Society of Magdeburg is one of the oldest associations of physicians in the territory of the German language. It was founded in 1848 following the discussions between the aspiring natural-scientifically orientated schools and the members of the medical profession who clung to the old habits of therapy which for the largest part developed from mysticism and symbolism. The society soon gained a scientific importance which transgressed the closer territorial boundaries. Distinguished representatives of medical science and practice were and are members of this society. As is was already in the past, the society is nowadays again a place of scientific meeting and postgraduate medical training, whereby it has retained its traditional progressive and interdisciplinary character and will be understood as the uniting tie for the whole medicine which now tends to frittering.
Germany↗
Comparison of different markers on blood lymphocytes of chronic lymphocytic leukemia.
Mononuclear cells (MNC) of 17 patients suffering from B chronic lymphocytic leukemia (B-CLL) were analysed by various immunological methods. The B cell nature of CLL cell was determined by classical tests (MRBC-rosette-test, immunofluorescence test for detection of membrane bound immunoglobulins). The cytochemical detection of the new T-cell marker dipeptidyl peptidase IV (DP IV) was found to be suitable for the characterization of B-CLL. The B-CLL cells showed granular pattern of alpha-naphthylacetate esterase (ANAE) reaction and binding of the monoclonal pan T antibody BL-T2. These non typical reactions for normal B lymphocytes can be used for differential diagnosis of B-CLL in combination with other reliable T cell markers. Avoiding the separation of T cells, the mixed rosette assay was used to enumerate Fc-IgG-receptor bearing T(TG) and non T cells. Both cell populations were found to be significantly elevated in MNC of B-CLL.
Aged↗
[Folic acid deficiency anemia caused by therapy in chronic renal insufficiency].
The turbidimetric determination of folic acid concentration in serum and erythrocytes was made by means of a spectrophotometer multiscan in 35 conservatively treated patients with chronic renal failure with a minimum creatine retention of 309 mumol/l and in 63 hemodialysed patients with terminal renal insufficiency. The result showed a statistically significant diminution of serum folic acid concentration in those patients treated in a conservative manner and a significant diminution of plasmatic and erythrocytic folate++ activity in patients under hemodialysis. There was a correlation between the folic acid concentration and the hemoglobin level in both groups of patients, whereas there was no correlation to the number of leukocytes and thrombocytes. A protein deficiency diet or loss of dialysis through the capillary membrane could be found to be the cause for the loss of folic acid. The possibility of folate++ substitutive therapy and its performance was discussed and recommended for selected indications.
Adult↗