[Interdisciplinary management of infections with multidrug resistant Staphylococcus aureus strains].
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Anti-Bacterial Agents↗
Biomedical subjects
C Langer
Publications and source records attributed to C Langer.
Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation.
Malignant pleural mesothelioma (MPM) is a generally fatal disease with no standard treatment. There are encouraging reports using intraperitoneal chemotherapy to treat peritoneal mesotheliomas and intrapleural chemotherapy (IPC) to treat malignant pleural effusions. Our objective was to evaluate the efficacy of IPC after subtotal pleurectomy. Between 1988 and 1992, 20 consecutive patients with diffuse MPM limited to one hemithorax underwent subtotal pleurectomy. Thirteen patients with biopsy-proven MPM known prior to thoracotomy were enrolled in a phase II combined modality protocol consisting of perioperative intrapleural cisplatin (100 mg/m2) and ara-C (1,200 mg) after subtotal pleurectomy, followed by systemic cisplatin (50 mg/m2/week x 8) and mitomycin-C (8 mg/m2, days 1 and 36). Seven patients with MPM could not be enrolled because their diagnosis was made post-thoracotomy. These patients underwent subtotal pleurectomy with (n = 4) or without (n = 3) adjuvant radiation (4,500-5,000 cGy in 3 patients, 2,100 cGy in 1 patient). One of three patients who developed chemotherapy-related nephrotoxicity died, the only treatment-related mortality. All 3 patients requiring postoperative readmission received IPC. Significant morbidity did not occur in patients not receiving chemotherapy. Median survival and time to progression were significantly longer in patients not receiving IPC (21 vs. 9 months, P = 0.04; 12 vs. 6 months, P = 0.01). In conclusion, intrapleural and postoperative systemic chemotherapy resulted in significant toxicity and did not improve survival in our patients who underwent subtotal pleurectomy for MPM.
Aged↗
Generation of pre-beta 1-HDL and conversion into alpha-HDL. Evidence for disturbed HDL conversion in Tangier disease.
HDL encompasses several apoA-I-containing particles that differ by size and show pre-beta- or alpha-mobility on agarose gel electrophoresis: pre-beta 1-LpA-I, pre-beta 2-LpA-I, pre-beta 3-LpA-I, alpha-LpA-I2, and alpha-LpA-I3. The quantitatively minor subclass pre-beta 1-LpA-I serves as an initial acceptor of cell-derived cholesterol. In this study, we generated a pre-beta 1-LpA-I-like particle in vitro by the incubation of biotinylated apoA-I with cholesterol-loaded macrophages. Both native pre-beta 1-LpA-I and in vitro-generated pre-beta 1-LpA-I were indistinguishable from lipid-free apoA-I by two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis but exhibited a different size upon gel filtration. In vitro-generated biotin-pre-beta 1-LpA-I took up twofold to threefold more [3H]cholesterol from labeled fibroblasts during a 1-minute pulse incubation than lipid-free apoA-I. The in vitro conversion of biotin-pre-beta 1- LpA-I was investigated in the presence of plasmas of healthy probands and patients with Tangier disease, with apoA-I deficiency, and with lecithin-cholesterol acyltransferase (LCAT) deficiency. Incubation of biotin-pre-beta 1-LpA-I with plasmas either from normoalphalipoproteinemic probands or from a patient with apoA-I deficiency generated a biotinylated particle with the size and electrophoretic mobility of alpha-LpA-I2. This conversion was sensitive to heating at 56 degrees C but not to the removal of calcium. Inhibition of LCAT by dithiobisnitrobenzoic acid led to the formation of alpha-LpA-I3 instead of alpha-LpA-I2.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[General practice of acute inpatient treatment of mania. Retrospective comparative study of 100 patients at each of 2 psychiatric centers].
We reviewed the literature regarding acute therapy of manic patients and compared these recommendations with actual practice by reviewing 399 therapies in 100 patients each from two psychiatric care centres between 1975 und 1991. Higher age, more serious disease and a higher percentage of compulsory commitments are typical of patients treated in institutions with a mandatory admission policy as compared to university clinics, which are not compelled to admit patients. The treatment methods practised in both centres deviated greatly from recommendations in the literature. In spite of widespread therapeutic recommendations, lithium and carbamazepin are seldom employed for acute treatment; neuroleptic agents were preferred for all grades of severity. Combinations of more potent antipsychotics with more sedative neuroleptics were preferred. In contrast, the chosen substances, the preferred combinations and the application form varied considerably. The state mental hospital preferred haloperidol and levomepromazin; in the university clinic clozapin and perphenazineoenanthate were important adjuncts. Both clinics remained in the low therapeutic range of dose recommendations. There were no statistically meaningful differences with regard to either the total amount of chlorpromazine equivalents applied or the duration of inpatient care. In the first one-tenth of the total treatment period, 85% of the maximal dose reached in the second tenth is already given. A continual reduction begins thereafter, until app. 40% of the peak dose in reached. Active treatment of side effects as well as more common use of depot neuroleptics in order to minimize custodial treatment, may explain the lower number of compulsory admissions in the university hospital. Extreme interindividual differences in both dosage and length of stay help in elucidating the apparently contradictory results of comparative investigations with small patient groups. Previous treatments have little or no predictive value due to large intraindividual variations.
Adult↗
Ifosfamide, carboplatin, and etoposide plus granulocyte-macrophage colony-stimulating factor: a phase I study with apparent activity in non-small-cell lung cancer.
PURPOSE: A phase I trial was performed to evaluate the feasibility of escalating the dose of etoposide in dose-intensive ifosfamide, carboplatin, and etoposide (ICE) with granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS: Twenty-four patients were entered between November 1990 and November 1991. Patients received ifosfamide 5 g/m2 by continuous infusion over 48 hours, carboplatin 400 mg/m2 by intravenous bolus, and GM-CSF 5 micrograms/kg/d subcutaneously from day 4 until neutrophil recovery. The etoposide dose was escalated, with six patients receiving 300 mg/m2 total dose (level 1), six receiving 600 mg/m2 (level 2), three receiving 900 mg/m2 (level 3), and five receiving 1,200 mg/m2 (level 4). Level 4B consisted of three patients who received etoposide 1,200 mg/m2 and GM-CSF 10 micrograms/kg/d. Cycles were repeated every 21 days. The maximum-tolerated dose (MTD) was prospectively defined as the dose level at which the next higher level produced greater than 7 days of grade 4 myelosuppression in two or more of six patients. RESULTS: Twenty-three patients were assessable. The median duration of neutropenia was < or = 7 days on cycle 1 at all dose levels. The initial criteria for determination of the MTD was never achieved. However, seven of eight patients treated at levels 4 and 4B required hospitalization for neutropenic fever on cycle 1 of therapy, with three of four septic events occurring at these levels. Cumulative thrombocytopenia occurred at all dose levels, with > or = 50% of patients requiring platelet transfusions on cycle 3. This became the dose-limiting toxicity above level 3. The overall response rate was 48%, with 11 of 23 objective responses, including two complete responses (CRs). Seven of 11 (64%) patients with non-small-cell lung cancer (NSCLC) responded, including one CR. Two of four (50%) heavily pretreated non-Hodgkin's lymphoma (NHL) patients responded, with one CR. CONCLUSION: The addition of GM-CSF to a dose-intensive ICE regimen permitted dose escalation of etoposide to 900 mg/m2, with cumulative thrombocytopenia as the dose-limiting toxicity. Carboplatin dosing by the area under the curve (AUC) may minimize thrombocytopenia. This appears to be an active regimen for patients with NSCLC and refractory NHL.
Adult↗
Mutation of monofunctional 6-phosphofructo-2-kinase in yeast to bifunctional 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase.
We have shown previously that 6-phosphofructo-2-kinase in yeast has negligible fructose-2,6-bisphosphatase activity even though resembling in part of its C-terminal sequence the phosphatase domain of the bifunctional liver enzyme. Here we show that exchanging Ser-404 to His-404 in the yeast peptide creates a bifunctional enzyme with a fructose-2,6-bisphosphatase activity involving a phosphoprotein intermediate. Like mammalian bifunctional enzymes, the His-404 mutant protein is readily phosphorylated by fructose 2,6-P2 with a half-saturation of 0.4 microM, the same Km value as for its fructose-2,6-bisphosphatase activity. Protein phosphorylation by the C-subunit of cAMP-dependent protein kinase, presumably at a C-terminal consensus site, increases the Km value to 1.5 microM. The newly created fructose-2,6-bisphosphatase is inhibited competitively by its product fructose 6-P with a K(i) of 0.6 mM. No effect of the His-404 mutation was found on 6-phosphofructo-2-kinase activity, in line with the mutant yeast enzyme having independent kinase and phosphatase domains, like its mammalian wild-type counterparts. The results would fit with the evolution of the PFK26 gene having involved fusion between kinase and phosphatase genes--as proposed for the mammalian enzyme--but with accompanying or later silencing of the fructose-2,6-bisphosphatase activity.
Animals↗
Prostanoids inhibit release of endogenous norepinephrine from rat isolated trachea.
Prostanoids, of epithelial origin, are known as modulators of several processes in the airways. The present study examined whether prostanoids are involved in the local control of sympathetic neurotransmission. The release of endogenous norepinephrine from rat isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine, and tyrosine. In different series of experiments, indomethacin (3 mumol/L) increased the evoked release of endogenous norepinephrine by 70 to 80%. In the presence of indomethacin, prostaglandin E2 (PGE2) and several prostanoid receptor agonists inhibited the evoked release of norepinephrine in a concentration-dependent manner, maximally by 60 to 70%. According to the concentration producing 35% inhibition of norepinephrine release (half-maximal effect), the following rank order of potencies was observed (EC35): nocloprost (8 nmol/L), sulprostone (30 nmol/L), PGE2 (308 nmol/L), iloprost (2 mumol/L), and U46619 (> 10 mumol/L). The EP1 receptor antagonist AH 6809 (3 mumol/L) had no effect on the evoked norepinephrine release and did not affect the inhibitory effect of 1 mumol/L of sulprostone. In the absence of indomethacin, the inhibitory effect of PGE2 was similar to that observed in the presence of indomethacin. After removal of the epithelium, the evoked norepinephrine release was markedly reduced. However, no significant effect of indomethacin was observed in epithelium-denuded tracheae. In conclusion, norepinephrine release in the rat trachea is inhibited via prostaglandin receptors that have the pharmacologic characteristics of the EP3 subtype. Endogenous eicosanoids, most likely of epithelial origin, are involved in the local control of the release of norepinephrine.
Animals↗
Cutaneous malakoplakia simulating relapsing malignant lymphoma.
This report describes the case of a 42-year-old man with malignant lymphoma, diffuse large non-cleaved cell type, who developed cutaneous malakoplakia in the left groin. The patient had widespread lymph node involvement, including a left inguinal mass which was clinically thought to represent recurrent lymphoma. The inguinal mass failed to regress after chemotherapy and irradiation, although lymphoma in other sites responded to chemotherapy. A skin biopsy of the area showed an ulcer and an abscess involving the dermis and subcutaneous tissue. Microscopically, a diffuse infiltrate of foamy histiocytes was seen with numerous intracellular and extracellular, round and laminated bodies. Some of these bodies had a "targetoid" appearance, stained strongly with von-Kossa's calcium stain and showed the typical appearance of Michaelis-Gutmann bodies by electron microscopy. Cultured monocytes from the peripheral blood of the patient showed ultrastructural features similar to their tissue counterparts, suggesting a systemic involvement of the monocyte macrophage lineage. This case represents an unusual presentation of malakoplakia of the skin associated with relapsing malignant lymphoma in a patient on immunosuppressive drugs.
Adult↗
[Death in a neurosurgical intensive care unit. Analysis of 109 deceased intensive care patients].
A retrospective study was performed on 109 patients who died in the neurosurgical ICU. We investigated the problem of outcome prediction in relation to diagnosis, status at admission and several risk factors. We analysed the meaning of diagnostical and therapeutical treatment and compared the clinical diagnosis to the neuropathological findings.
Adult↗
[Anamnestic and psychopathologic studies of obsessive-compulsive patients].
Twenty-eight patients, that is 0.8% of all 3,225 patients admitted between 1981 and 1986 in the Free University of Berlin, Department of Psychiatry, had a primary diagnosis of obsessive-compulsive disorder (ICD-9: 300.3). These patients were compared with random samples of equal size (N = 28) of schizophrenic psychoses paranoid type (ICD 295.3), manic depressive psychoses depressed type (ICD 296.1) and neurotic depressions (ICD 300.4) using an AMDP-based multiaxial diagnostic description. It turned out, that although obsessive-compulsive patients were best discriminated from the other clinical groups by their typical symptoms, they were characterized likewise by other psychopathological, especially depressive symptoms. In view of the course of obsessive-compulsive disorder, the findings were compatible with those of other reports. Beyond it, a subgroup of patients with relatively unfavourable course could be described by AMPD-items.
Adolescent↗
[Decubitus prevention and therapy].
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Bedding and Linens↗
[The psychological situation of nursing personnel in intensive care units. Observations and experiences].
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Family↗
[Scale formation in the AMDP (Society for Methodology and Documentation in Psychiatry) system].
The psychopathological and somatic symptoms documented by the AMDP-system on the admission of 1654 patients to the Psychiatric Clinics of the Universities in München und 659 patients in Berlin were factor analyzed. Eight factors could be extracted which describe the psychopathology on eight syndrome-scales. These factors could be cross-validated by factor analyses on random samples. In correspondence with the factors of the AMP-system the following syndromes were found: paranoid-hallucinatory, depressive, psycho-organic, manic, hostility, autonomic, apathy, obsessive-compulsive. For each of the 70 items which were associated with a factor we computed the percentage occurrence and item-scale-intercorrelations, for each of the eight syndrome-scales reliability-coefficients, intercorrelations and T-transformations. For further data-reduction second-order-factors were also computed.
Adult↗
The syndrome scales in the AMDP-System.
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Adult↗
[Arthrogenic congestive syndrome].
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Adult↗
[Special diagnostic and therapeutic procedure for the incomplete form of primary varicosis].
The difference between the incomplete and complete form of the primary varicosis of the internal saphenous vein is that the saphenofemoral valve is still intact in the incomplete form. There are two types of the incomplete form, one caused by a perforating vein and the other by a lateral branch of the saphenous vein. The preoperative diagnostic procedure is particularly important for the optimal choice of treatment.
Humans↗
[A statistical comparison of the different factor analyses of the AMP-system (author's transl)].
The intercorrelations of five different factor-analytically derived syndrome solutions of the AMP-system were computed. The syndromes were based on the psychopathological symptoms of 2,269 patients on admission to the psychiatric clinic of the Free University of Berlin. The syndromes which were similar in content in the solutions of different clinics could be shown to intercorrelate quite highly. Only the different syndromes of stupor and obsession-compulsion did not show the same high degree of similarity. Between the syndromes of the solution of one clinic as well as between the solutions of different clinics high intercorrelations were computed comparing non-corresponding syndromes; this could be demonstrated for the syndromes of mania with hostility and of apathy with stupor and depression. For building syndromes in the AMDP-system in the near future the aim for independence of the syndromatic scales seems to be important.
Factor Analysis, Statistical↗