Catamenial epilepsy and menopause.
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Epilepsy↗
Biomedical subjects
J Bauer
Publications and source records attributed to J Bauer.
The greater acceptance and utilization of nurse practitioners.
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Clinical Competence↗
[Tamoxifen or tamoxifen in combination with chemotherapy in adjuvant therapy of breast carcinoma. Results of a multicenter randomized study].
UNLABELLED: Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1, M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q 28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on tamoxifen plus CMF pts, preferably postmenopausal. RESULTS: Grade of toxicity according to WHO criteria was not higher then two in both arms. Toxicity both haematological and non-haematological was higher in the group treated with chemotherapy (0 vs 32 resp. 20%) except weight gain (52% in both group). After median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen plus CMF pts were observed (p = NS). The projected 3-y DFS is 92% for tamoxifen and 88% for tamoxifen plus CMF (p = NS). The 3-y OS is 88% for tamoxifen and 80% for tamoxifen plus CMF pts (p = NS). CONCLUSIONS: Both regimens are equally effective with higher toxicity in the group with combined chemo- and hormonal therapy.
Aged↗
Synthesis, characterization, and structural and theoretical analysis of Gd4B3C4: a novel rare earth metal borocarbide containing two different boron-carbon arrangements.
The synthesis by arc-melting techniques, the single-crystal X-ray structure, and the theoretical analysis of Gd4B3C4 are reported. It crystallizes in the triclinic space group P1 with a = 3.637(2) A, b = 3.674(2) A, c = 11.859(5) A, alpha = 93.34(5) degrees, beta = 96.77(5) degrees, gamma = 90.24(5) degrees, and Z = 1. In this structure, the boron and carbon atoms form two different types of nonmetal arrangements: 1-D (BC)infinity branched chains and finite (0-D) linear CBC "molecular" units. Gd4B3C4 is the first characterized member of the rare earth metal borocarbide series in which both 1-D and "molecular" 0-D nonmetal atom systems coexist. From the structural and theoretical analysis, the following formal charge distribution can be proposed within the ionic limit: (Gd3+)4(BC2(5-)(BC3-)2.e-. Tight-binding calculations suggest that the excess electron in the ionic limit is mainly localized on the Gd atoms (at the bottom of the 5d band), while LAPW calculations favor its localization on the (BC)infinity chain. The bonding within this compound is fully analyzed and compared to other members of the rare earth metal borocarbide series.
Journal Article↗
Rhesus monkeys are highly susceptible to experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein: characterisation of immunodominant T- and B-cell epitopes.
Eight rhesus monkeys with different MHC backgrounds were immunized with myelin oligodendrocyte glycoprotein (MOG). All developed severe experimental autoimmune encephalomyelitis associated with large inflammatory foci and extensive demyelination. T-cell autoreactivity to MOG was directed against three main epitopes encompassed within amino acids 4-20, 35-50 and 94-116, of which two are also immunodominant epitopes for the autoimmune T cell response to MOG in patients with MS. A strong B cell response to MOG was observed in all monkeys and major epitopes recognized were located within amino acids 4-26, 24-46 and 44-66/54-76.
Animals↗
Serum androgens return to normal after temporal lobe epilepsy surgery in men.
BACKGROUND: Epileptic discharges from the temporal lobe may influence the release of hormones from the hypothalamic-pituitary axis. If epilepsy surgery influences the underlying epileptic disorder one might expect serum hormone concentrations to return to normal following surgery. PATIENTS: Twenty-two men with epilepsy aged 25 to 48 years (mean, 34.9 years) were investigated before surgery and at 3, 6, and 12 months after surgery. Medication (all patients received carbamazepine) was maintained following surgery. METHODS: Hormone measurements included luteinizing hormone, follicle stimulating hormone, estradiol, testosterone, free testosterone, androstenedione, prolactin, dehydroepiandrosterone sulfate, cortisol, growth hormone, and sex hormone-binding globulin. These hormone levels were compared with those of 105 healthy men (mean age, 33.9 years). RESULTS: Fourteen of the 22 patients (63.6%) achieved total seizure control following epilepsy surgery. The 14 patients with successful seizure control entered further analysis. Before surgery these patients' free testosterone and androstenedione concentrations were significantly lower compared with healthy men. In seven of the 14 patients a significant increase of hormone serum concentrations could be demonstrated for testosterone, free testosterone, and androstenedione. Laterality of epileptic focus, enzyme-inducing medication, stress, and the decreasing number of patients during the follow-up did not correlate with the finding of a normalization of serum androgens. PATIENTS without complete seizure control did not show an increase in serum androgen concentrations. CONCLUSION: Successful temporal lobe epilepsy surgery may lead to a normalization of serum androgen concentrations in men with epilepsy.
Adult↗
An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains.
To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation.
Journal Article↗
The major protein import receptor of plastids is essential for chloroplast biogenesis.
Light triggers the developmental programme in plants that leads to the production of photosynthetically active chloroplasts from non-photosynthetic proplastids. During this chloroplast biogenesis, the photosynthetic apparatus is rapidly assembled, mostly from nuclear-encoded imported proteins, which are synthesized in the cytosol as precursors with cleavable amino-terminal targeting sequences called transit sequences. Protein translocon complexes at the outer (Toc complex) and inner (Tic complex) envelope membranes recognize these transit sequences, leading to the precursors being imported. The Toc complex in the pea consists of three major components, Toc75, Toc34 and Toc159 (formerly termed Toc86). Toc159, which is an integral membrane GTPase, functions as a transit-sequence receptor. Here we show that Arabidopsis thaliana Toc159 (atToc159) is essential for the biogenesis of chloroplasts. In an Arabidopsis mutant (ppi2) that lacks atToc159, photosynthetic proteins that are normally abundant are transcriptionally repressed, and are found in much smaller amounts in the plastids, although ppi2 does not affect either the expression or the import of less abundant non-photosynthetic plastid proteins. These findings indicate that atToc159 is required for the quantitative import of photosynthetic proteins. Two proteins that are related to atToc159 (atToc120 and atToc132) probably help to maintain basal protein import in ppi2, and so constitute components of alternative, atToc159-independent import pathways.
Amino Acid Sequence↗
Application of binary buffer systems to free flow cell electrophoresis.
The applicability of free flow electrophoresis (FFE) was expanded towards processing of sensitive cells. The chamber medium was adjusted to a physiologic pH of 7.35 by a mixture of N-(2-hydroxyethyl)piperazine-N'-(3-propanesulfonic acid) (EPPS) and 2,2-bis(hydroxymethyl)-2,2'2"-nitrilotriethanol (BISTRIS). These substances proved to be nontoxic to sensitive cells such as human smooth muscle or thyroid cells. They enhanced the electrical conductivity of the medium only slightly so that a new cell electrophoresis separation medium could be prepared, which contained 30 mM NaCl together with or without 1 mM CaCl2 but did not generate problems of overheating the fluid. Suspended in this medium, human smooth muscle cells as well as human thyroid carcinoma cells remained viable single cells for at least 120 min. After this period they could be recultured to form monolayers. If electrophoresed in the Octopus preparative FFE device, they migrated as single cells and did not clot; therefore, their electrophoretic behavior could be determined exactly.
Cell Separation↗
Establishment and characterization of the follicular thyroid carcinoma cell line ML-1.
The present study focuses on the establishment and characterization of a new follicular thyroid carcinoma cell line. The human cell line ML-1 was derived from a dedifferentiated follicular thyroid carcinoma relapse, which progressed despite preceding surgery followed by two radioiodine therapies. More than 90% of the cells of this line express thyroglobulin, chondroitin sulfate, and vimentin antigens, but only about 70% show cytokeratin filaments and a negative surface charge density such as human erythrocytes. More importantly, cells of this line are able to take up iodine and/or glucose both in vitro and in vivo and to secrete thyroglobulin, chondroitin sulfate, and fibronectin into the interstitial space. In addition, triiodothyronine is released constitutively into culture supernatants. Moreover, it is also suitable for xenotransplantation studies because it is tumorigenic in NMRI nude mice in vivo. The cell line forms tumors with follicular structures when transplanted to nude mice. Due to these unique features the ML-1 cell line can be considered as a very suitable test model for pharmacological and cell biological studies. Since chemicals may interfere with the production of thyroid hormones, this cell line represents also a tool for toxicological investigations.
Adenocarcinoma, Follicular↗
[Therapy of generalized tonic-clonic status epilepticus in adulthood].
If continuous seizure activity lasts longer than 5 minutes generalized tonic-clonic seizures require prompt treatment, if significant morbidity and mortality are to be avoided. The mortality varies (mean: 20%) depending on patient age and etiology. Control of status epilepticus is achieved by benzodiazepines in about 80% of cases: Lorazepam is recommended due to its longer-acting effects on the central nervous system. To maintain the anticonvulsive effect phenytoin is usually administered intravenously. Fosphenytoin (not approved in Germany) has advantages over phenytoin, because it can be given three times more rapidly and produces fewer side effects. The IV use of valproic acid in status epilepticus seems to be promising, but needs further evaluation. There is no generally accepted treatment protocol for the therapy of persistent seizure activity lasting more than 60 minutes (i.e., refractory status epilepticus). Usually phenobarbital, or general anesthesia with thiopental or pentobarbital are treatment recommendations. In recent reports, the administration of midazolam or propofol proved to be effective and well-tolerated.
Anticonvulsants↗
[Topiramate (Topamax). Pharmacological characteristics and current use in epilepsy treatment].
Topiramate (Topamax) has been registered since July 1998 and has market authorization for the Federal Republic of Germany as an additive drug for the treatment of patients (age 12 or older) suffering from intractable partial and secondarily generalized seizures. The anticonvulsant effect of topiramate is based on three mechanisms: (a) modulating the blocking of the Na channels activated by voltage, depending on status, (b) potentiation of GABAA-mediated inhibiting neurotransmission, and (c) inhibition of excitatory neurotransmission by blocking APMA glutamate receptors. Topiramate exhibits a substantial anticonvulsive effect on partial seizures both with and without secondary generalization. The median reduction in seizure frequency using topiramate as adjunct therapy was 44%. In 44% of patients, seizure frequency was reduced by more than 50%, and seizure reduction was more than 75% in nearly half of these (i.e., in 21% of all patients), while 5% of patients remained completely free of seizures. Adverse events most often caused central nervous disturbances. Weight loss, the development of renal calculi, and impairment of cognitive functions may occur. It is recommended to start therapy with topiramate at a daily dosage of 25 mg, increasing by 25 mg every week up to 200-400 mg/day but not exceeding 1000 mg/day.
Anticonvulsants↗
Prefrontal cortical hypometabolism during low-dose interferon alpha treatment.
OBJECTIVE: To evaluate prospectively interferon alpha (IFN-alpha) associated effects on cerebral glucose metabolism and its correlation to neuropsychiatric symptoms during low-dose IFN-alpha-treatment. METHODS: Eleven patients treated with low-dose IFN-alpha for chronic hepatitis C were prospectively evaluated by neuropsychiatric tests and cerebral [18F]deoxyglucose positron emission tomography (FDG-PET) before and in the 12th week of treatment. PET images were spatially normalized, corrected for variance in global activity and pixel-based t-statistics were calculated for each set of PET scans using SPM96 software. Pixel-cluster with P<0.001 for hypo- or hypermetabolism were displayed in parametric images. Covariance analysis with neuropsychiatric tests was calculated for each cluster. RESULTS: In week 12 of IFN-alpha treatment, significant hypometabolism with a decrease of local activity ranging from 8 to 12% was found in all patients bilaterally in the prefrontal cortex (BA 9), which correlated in a covariate analysis with changes in depression score as measured by Beck's Depression Inventory. Additionally, hypermetabolism with a maximum increase in local activity of 6-8% was seen in all patients in putamina as well as the left occipital region (BA 18). Before IFN-alpha treatment, only 1/11 patient showed depressive symptomatology. After 3 months of treatment, 6/11 patients were classified as having mild to moderate depressive symptoms (P<0.1; Wilcoxon test). CONCLUSIONS: Low-dose IFN-alpha therapy is associated with significant prefrontal hypometabolism. This hypometabolism covaried with depression score, but was even found in clinically non-depressed patients. These findings may reflect a possible predisposing factor for IFN-alpha associated neuropsychiatric syndromes and might contribute to a pathophysiological model of affective disorders, as endogenous IFN-alpha levels are elevated in a subset of psychotic patients during acute disease.
Adult↗
A new primate model for multiple sclerosis in the common marmoset.
Experimental autoimmune encephalomyelitis (EAE) in outbred marmoset monkeys (Callithrix jacchus) is a recently developed nonhuman primate model of multiple sclerosis. Here, Bert 't Hart and colleagues compare this model to EAE in rhesus monkeys, highlighting autoimmune mechanisms in CNS inflammation and demyelination, including the role of major histocompatibility complex restriction and preclinical evaluation of innovative immunotherapies.
Acute Disease↗
Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women.
A prospective cohort analysis of premenopausal women with focal epilepsy was conducted in order to determine whether polycystic ovary syndrome (PCOS) is a common finding in women treated with antiepileptic drugs (AED). This study was carried out in 93 of 150 women (aged between 20 and 53 years; mean, 34.3 years) with chronic focal epilepsy consecutively cared for at the Department of Epileptology, University of Bonn: 38 were receiving one AED (18 valproate, 20 carbamazepine), 36 more than one drug, and 19 were without medication. Patients were followed-up for 6 months. PCOS was defined as hyperandrogenism (testosterone concentration, > 0.7 ng/ml) combined with oligomenorrhoea (cycle length, > 35 days) or amenorrhoea. PCOS was identified in two out of 19 (10.5%) patients receiving no medication; in four of 38 (10.5%) of patients receiving monotherapy, and in none of the patients receiving more than one AED. The incidence of PCOS in patients treated with valproate monotherapy (11.1%) was similar to that in patients treated with carbamazepine (10%) and also to that in patients not treated with AEDs. The results of this study suggest that the manifestation of PCOS in women with focal epilepsy is not related to the administration of valproate or carbamazepine.
Adult↗
Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex.
OBJECTIVES: To define the maximum tolerated dose (MTD), the toxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. PATIENTS AND METHODS: Fourteen patients with advanced solid tumors not responsive to previous antitumor treatments received BBR 3464 on a daily x 5 schedule every twenty-eighth day. The drug was given as a one-hour infusion with pre-and post-treatment hydration (500 ml in one hour) and no antiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. A modified accelerated titration escalation design was used. Total and free platinum (Pt) concentrations in plasma and urine were assessed by ICP-MS on days 1 and 5 of the first cycle. RESULTS: Dose was escalated four times up to 0.17 mg/m2/day. Short-lasting neutropenia and diarrhea of late onset were dose-limiting and defined the MTD at 0.12 mg/m2. Nausea and vomiting were rare, neither neuro- nor renal toxic effects were observed. BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-life of several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 were higher than on day 1, indicating drug accumulation. Approximately 10% of the equivalent dose of BBR3464 (2.2%-13.4%) was recovered in a 24-hour urine collection. CONCLUSIONS: The higher than expected incidence of neutropenia and GI toxicity might be related to the prolonged half-life and accumulation of total and free Pt after daily administrations. Lack of nephrotoxicity and the low urinary excretion support the use of the drug without hydration. The single intermittent schedule has been selected for clinical development.
Adolescent↗
Response and palliation in a phase II trial of gemcitabine in hormone-refractory metastatic prostatic carcinoma. Swiss Group for Clinical Cancer Research (SAKK).
BACKGROUND: In a phase II trial, 43 patients with hormone-refractory prostate cancer were treated with gemcitabine at a dose of 1,200 mg/m2 over 2 hours (later decreased to 1,000 mg/m2 due to hematological toxicity) on days 1, 8 and 15 of a 28 day cycle. PATIENTS AND METHODS: Inclusion criteria were proven tumor progression after hormonal treatment and increased PSA levels, a WHO PS < or = 2, adequate bone marrow reserve, liver and renal function and age < or =, 80 years. Response criteria were based on PSA levels (CR: normalization of PSA, PR: > 50% decrease). Quality of life (QL) was assessed with the EORTC QLQ-C30 on day 1 of each treatment cycle and on day 8 of the first cycle (range of scales 0-100). Physician-rated pain intensity and use of pain medication were assessed at the same timepoints. RESULTS: Hematological toxicity of gemcitabine led to a dose-reduction in 48% of all cycles. Three of forty-three patients (RR = 7%) showed a PSA response: one CR and three PR with time to treatment failure of 8.7, 6.6 and > or = 9.3 months. Seven patients (16%) had stable disease (NC) for a median duration of 7.1 months (range 6.1-11.7 months). There was one case with objective regression of lymph node metastases. Patients reported a considerably impaired health status/QL (n = 41, median = 50) and severe fatigue (n = 41, median = 55.6) at baseline, with no change under treatment. Pain (QLQ-C30) was also severe at baseline (N=41, median=50) but was improved at the end of cycles 1 (n = 33, median change = -16.7, P = 0.0002), 2 (n = 19, median change = -33.3, P = 0.0006), 3 (n = 14, median change = -16.7, P = 0.06) and 4 (n = 9, median change = -33.3, P = 0.04). Patient-rated pain and use of analgesics as combined endpoint yielded palliation for at least 8 weeks in 14 patients (32%). Nine of these patients showed at least stable disease (CR/PR or NC by PSA level), five indicated a benefit in spite of progressive disease. CONCLUSIONS: Gemcitabine in the dose and schedule indicated above has a significant beneficial impact on pain in patients with hormone-refractory prostatic carcinoma despite its limited activity in terms of PSA response and considerable, especially hematological, toxicity.
Adenocarcinoma↗
Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: a multicentric phase I-II study.
BACKGROUND: The combination of anthracyclines and taxanes is currently considered the first choice chemotherapy in advanced breast cancer (ABC) and considerable emphasis has been placed on programs exploring the safest and most efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m2 and docetaxel (D) 75 mg/m2 as first-line chemotherapy in ABC. PATIENTS AND METHODS: A total of 70 patients were entered in the initial dose-finding study (20 patients) and in the subsequent extended phase II trial (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity observed in the phase I study at a median cumulative E dose of 480 mg/m2. A maximum of eight cycles of the combination was allowed, and cardiac function was monitored at baseline and after every second course by echocardiography. RESULTS: Overall, the median number of cycles administered with the combination was 4 (range 3-8). Neutropenia was confirmed to be the main haematological toxicity, with granulocyte colony-stimulating factor (G-CSF) support required in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatient basis with oral antibiotics. Overall, the median cumulative dose of E, including prior adjuvant anthracyclines, was 495 mg/m2 (range 270-1020 mg/m2). One patient who received adjuvant E together with radiotherapy to the left chest wall developed fully reversible clinical signs of cardiotoxicity and a significant decrease of LVEF to 35% after a cumulative E dose of 870 mg/m2, with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 evaluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A comparable antitumour activity of 71% was reported in the group of patients with a prior adjuvant chemotherapy with anthracyclines. After an overall median follow-up time of 22 months (range 4-39+), the median time to progression (TTP) was 4.5 months and the median duration of response was 8 months (range 3-16). No pharmacokinetic (Pk) interaction could be demonstrated between E and D when given simultaneously and sequentially with a one-hour interval. CONCLUSIONS: The combination of E and D in a multiinstitutional setting is an active and safe regimen in poor-prognosis patients with ABC. New combinations and schedules are worth considering in an attempt to further improve disease response and long-term control of the disease.
Adult↗