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1.
J Affect Disord ; 281: 228-234, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33338840

ABSTRACT

INTRODUCTION: Altered levels of acute-phase proteins are often described in different conditions in BD. Nevertheless, data on the association between lithium treatment and inflammatory markers in the long-term course of BD are still missing. The aim of the study was to examine the long-term course of BD concerning long-term lithium treatment, chronic inflammatory processes and symptom progression. Furthermore, the association between duration of lithium treatment and levels of hsCRP was explored. METHODS: 267 individuals (males= 139, females= 128) with BD were included. Duration of lithium treatment as well as symptom progression, defined as the increase in severity of symptoms, number of episodes a year and duration of episodes within a period of 1.5 years in the past and hsCRP were evaluated. RESULTS: Male individuals with symptom progression over time had significantly lower duration of lithium treatment compared to individuals without symptoms progression (U= 47.4, p=.037). There were significantly higher levels of hsCRP in male individuals with symptom progression compared to males without symptom progression (U= 47.5, p=.027). Further, there was a significant negative correlation between the duration of lithium treatment and hsCRP levels in the whole sample (r= -.276, p<.05). CONCLUSION: Our results show that an altered inflammatory state may be associated with a more severe illness course in BD. Further, a longer duration of lithium treatment may be associated with lower symptom progression. The shown association between hsCRP-levels and lithium treatment duration suggests a potential anti-inflammatory effect of lithium as a mediator of its significant positive outcome effect in BD.


Subject(s)
Bipolar Disorder , Lithium , Anti-Inflammatory Agents/therapeutic use , Biomarkers , Bipolar Disorder/drug therapy , Female , Humans , Lithium/adverse effects , Lithium Compounds/therapeutic use , Male
2.
Opt Express ; 28(12): 17934-17943, 2020 Jun 08.
Article in English | MEDLINE | ID: mdl-32679995

ABSTRACT

We theoretically and experimentally investigate Tamm plasmon (TP) modes in a metal/semiconductor distributed Bragg reflector (DBR) interface. A thin Ag (silver) layer with a thickness (55 nm from simulation) that is optimized to guarantee a low reflectivity at the resonance was deposited on nanoporous GaN DBRs fabricated using electrochemical (EC) etching on freestanding semipolar (2021¯) GaN substrates. The reflectivity spectra of the DBRs are compared before and after the Ag deposition and with that of a blanket Ag layer deposited on GaN. The experimental results indicate the presence of a TP mode at ∼ 454 nm on the structure after the Ag deposition, which is also supported by theoretical calculations using a transfer-matrix algorithm. The results from mode dispersion with energy-momentum reflectance spectroscopy measurements also support the presence of a TP mode at the metal-nanoporous GaN DBR interface. An active medium can also be accommodated within the mode for optoelectronics and photonics. Moreover, the simulation results predict a sensitivity of the TP mode wavelength to the ambient (∼ 4-7 nm shift when changing the ambient within the pores from air with n = 1 to isopropanol n = 1.3), suggesting an application of the nanoporous GaN-based TP structure for optical sensing.

3.
Opt Express ; 23(23): 29698-707, 2015 Nov 16.
Article in English | MEDLINE | ID: mdl-26698451

ABSTRACT

Hybrid optical antennas, comprising active materials placed in the gaps of plasmonic split-ring-resonators and nano-dimers, have been the subject of numerous recent investigations. Engineered coupling between the two plasmonic resonators is achieved by modulating the active material, enabling control over the near- and far-field electromagnetic properties. Here, using electromagnetics calculations, we study the evolving optical response of a hybrid metal-semiconductor-metal nanorod antenna as the semiconductor free charge carrier density is continuously varied. In particular, we demonstrate qualitatively new behavior arising from epsilon-near-zero properties in intermediately doped semiconductors. In agreement with optical nano-circuit theory, we show that in the epsilon-near-zero regime such a load acts as an ideal optical resistor with an optimized damping response and strongly suppressed electromagnetic scattering. In periodic arrays, or metasurfaces, we then show how to use these effects to construct high-efficiency nanophotonic intensity modulators for dynamically shaping light.

4.
Ann Oncol ; 20(9): 1522-1528, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19465425

ABSTRACT

BACKGROUND: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. PATIENTS AND METHODS: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m(2) and docetaxel (Taxotere) 75 mg/m(2) on days 1 and 22, followed by radiotherapy of 45 Gy (25 x 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m(2) and docetaxel 20 mg/m(2) weekly for 5 weeks, followed by surgery. RESULTS: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. CONCLUSIONS: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/therapy , Esophageal Neoplasms/therapy , Neoadjuvant Therapy , Adult , Aged , Carcinoma/mortality , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Digestive System Surgical Procedures , Docetaxel , Esophageal Neoplasms/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Radiotherapy , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome
5.
Psychopathology ; 42(2): 99-107, 2009.
Article in English | MEDLINE | ID: mdl-19225244

ABSTRACT

BACKGROUND: In our 2-year prospective study of 80 patients admitted consecutively to our clinic with an episode of acute vestibular neuritis, a total of 8 patients later developed a panic disorder according to DSM-III-R criteria. The goal of our analysis was to determine whether certain conflict patterns (e.g. in the area of autonomy vs. dependence) or deficient psychological structure could predict later panic disorder, as might be expected based on psychodynamic theory. SAMPLING AND METHODS: Between 4 and 8 weeks after the acute vestibular episode, we evaluated all patients using operationalized psychodynamic diagnostics (OPD). With the different axes of the OPD system, we were able to assess patients' experience of illness (Axis I), potential conflicts (Axis III), and psychological structure (Axis IV) in a semiquantitative manner. RESULTS AND CONCLUSIONS: Poor psychosocial integration, a lack of social support, a high burden of suffering, and moderate to severe impairment of self-experience were able to account for 32.1% (Nagelkerkes R(2)=0.321) of variance in the development of panic disorder over the course of 2 years. However, contrary to what might have been expected based on psychodynamic theory, patients who later developed a panic disorder did not exhibit any differences in their Axis III or IV scores compared to patients who remained psychologically healthy.


Subject(s)
Panic Disorder/epidemiology , Panic Disorder/psychology , Vestibular Neuronitis/epidemiology , Vestibular Neuronitis/psychology , Conflict, Psychological , Cost of Illness , Diagnostic and Statistical Manual of Mental Disorders , Disease Progression , Female , Humans , Male , Middle Aged , Panic Disorder/diagnosis , Prospective Studies , Psychology , Self Concept , Severity of Illness Index , Social Support , Time Factors , Vestibular Neuronitis/diagnosis
6.
Oncology ; 73(3-4): 228-37, 2007.
Article in English | MEDLINE | ID: mdl-18424887

ABSTRACT

BACKGROUND: We evaluated previously established regimens of capecitabine plus vinorelbine in older patients with advanced breast cancer stratified for presence versus absence of bone metastases. PATIENTS AND METHODS: Patients > or =65 years who had received no prior chemotherapy for advanced breast cancer received up to six 21-day cycles of vinorelbine 20 mg/m(2) i.v. on days 1 + 8 with oral capecitabine on days 1-14 (1,000 vs. 1,250 mg/m(2) daily in patients with vs. without bone involvement). RESULTS: Median age was 72 years in patients with bone metastases (n = 47) and 75 years in patients without bone metastases (n = 23). Response rates were 43% (95% confidence interval, CI, 28.3-58.8) and 57% (95% CI = 34.5-76.8), respectively. Median time to progression was 4.3 (95% CI = 3.5-6.0 months) and 7.0 months (CI = 4.1-8.3), respectively. Neutropenia was the most common toxicity, with grade 3/4 occurring in 43 and 39%, respectively. Pulmonary embolism was seen in 5 and grade 3 thrombosis in 3 patients. Other toxicities were mild to moderate. CONCLUSIONS: These regimens of capecitabine and vinorelbine are active and well tolerated in patients with advanced breast cancer > or =65 years. Response rates were comparable to published results. The lower capecitabine doses appeared appropriate given the advanced age, bone involvement and prior radiotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Aged , Aged, 80 and over , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Capecitabine , Cohort Studies , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Maximum Tolerated Dose , Skin Neoplasms/drug therapy , Skin Neoplasms/secondary , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
7.
Br J Surg ; 91(2): 142-5, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14760659

ABSTRACT

BACKGROUND: Carcinoma showing thymic-like elements (CASTLE) is a rare tumour of the thyroid of thymic origin. The histological appearance of this tumour may be similar to that of squamous cell carcinoma of the thyroid, but outcome associated with CASTLE is more favourable. METHODS: A systematic literature review was conducted for case reports on CASTLE. A text word search of the Medline database was made with a manual search of the citations from these references. Twenty-two case reports were found. RESULTS: In five patients with tumour-negative lymph nodes no local or distant recurrence was observed. Seventeen patients had unknown or involved lymph nodes. Two patients were excluded from further study: one had no follow-up and one was treated by irradiation only. Of the remaining 15, six had local, three had distant and two had local and distant recurrence. In patients with involved or unknown lymph node status, local recurrence was noted in one of five patients treated by surgery and irradiation, and in seven of ten patients treated by surgery alone. Irradiation or systemic chemotherapy was given to four patients with recurrent tumours, with variable response. CONCLUSION: CASTLE with tumour-negative lymph nodes has a low risk of recurrence and surgery without adjuvant therapy is sufficient. Radiotherapy seems indicated when lymph nodes are tumour positive and can be effective for recurrent tumours. In selected patients surgery for recurrent tumour can improve quality of life and outcome.


Subject(s)
Carcinoma, Squamous Cell/pathology , Thymus Neoplasms/pathology , Thyroid Neoplasms/pathology , Adult , Aged , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Tomography, X-Ray Computed
8.
Ann Oncol ; 13(1): 81-6, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11865814

ABSTRACT

BACKGROUND: Trimetrexate (TMTX) is a biochemical modulator of 5-fluorouracil (5-FU) and leucovorin (LV). Phase II trials have shown promising activity of 5-FU/LV/TMTX in patients with advanced colorectal cancer (ACC). This trial evaluated the effect of TMTX in combination with 5-FU/LV as first-line treatment in ACC. PATIENTS AND METHODS: Patients with ACC were randomised to receive either intravenous LV 200 mg/m2/5-FU 600 mg/m2 or TMTX 110 mg/m2 followed 24 h later by LV 200 mg/m2/5-FU 500 mg/m2 plus oral LV rescue. Both schedules were given weekly for 6 weeks every 8 weeks. Patients were evaluated for progression-free survival (PFS), overall survival (OS), tumour response, quality of life (QoL) and toxicity. RESULTS: A total of 365 patients were randomised. A statistically significant prolongation of median PFS was seen in patients treated with TMTX/5-FU/LV compared with 5-FU/LV (5.4 months versus 4.1 months, respectively; P = 0.03), and a trend towards a significant benefit for OS (13.4 months versus 10.5 months, respectively; P = 0.08). Tumour response, QoL and toxicity were comparable between the two arms. Diarrhoea was the most frequently occurring grade 3 or 4 toxicity (22% and 30%, respectively). CONCLUSIONS: The addition of TMTX to a weekly regimen of 5-FU/LV results in a small but significant improvement in PFS without adding toxicity or worsening QoL in patients with ACC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Trimetrexate/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/pathology , Disease Progression , Europe , Female , Fluorouracil/adverse effects , Humans , Leucovorin/adverse effects , Male , Middle Aged , Quality of Life , Survival Rate , Trimetrexate/adverse effects , Trimetrexate/pharmacology
9.
Clin Exp Dermatol ; 26(7): 592-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11696063

ABSTRACT

In recent years, the exposure of human skin to environmental and artificial UV irradiation has increased dramatically. This is due not only to increased solar UV irradiation as a consequence of stratospheric ozone depletion, but also to inappropriate social behaviour with the use of tanning salons still being very popular in the public view. Besides this, leisure activities and a lifestyle that often includes travel to equatorial regions add to the individual annual UV load. In addition to the common long-term detrimental effects such as immunosuppression and skin cancer, the photo-oxidative damage due to energy absorption of UV photons in an oxygenized environment leads to quantitative and qualitative alterations of cells and structural macromolecules of the dermal connective tissue responsible for tensile strength, resilience and stability of the skin. The clinical manifestations of UV/reactive oxygen species (ROS)-induced disturbances result in photoaged skin with wrinkle formation, laxity, leathery appearance as well as fragility, impaired wound healing capacities and higher vulnerability. Strategies to prevent or at least minimize ROS-induced photo-ageing and intrinsic ageing of the skin necessarily include protection against UV irradiation and antioxidant homeostasis.


Subject(s)
Connective Tissue/physiology , Fibroblasts/physiology , Skin Aging/physiology , Animals , Cellular Senescence/physiology , Estrogen Replacement Therapy , Female , Humans , Male , Matrix Metalloproteinases/metabolism , Mice , Mice, Transgenic , Reactive Oxygen Species/radiation effects , Skin Aging/drug effects , Skin Aging/pathology , Ultraviolet Rays
10.
J Photochem Photobiol B ; 63(1-3): 41-51, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11684450

ABSTRACT

The skin is increasingly exposed to ambient UV-irradiation thus increasing risks for photooxidative damage with long-term detrimental effects like photoaging, characterized by wrinkles, loss of skin tone and resilience. Photoaged skin displays alterations in the cellular component and extracellular matrix with accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) which deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in clinical and biochemical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be briefly discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS-induced photoaging.


Subject(s)
Skin Aging/radiation effects , Aging , Animals , Humans , Models, Biological , Reactive Oxygen Species/metabolism , Skin Aging/pathology , Solar Activity , Ultraviolet Rays/adverse effects
11.
Orv Hetil ; 142(27): 1457-8, 2001 Jul 08.
Article in Hungarian | MEDLINE | ID: mdl-11481909

ABSTRACT

The authors present a case of an adult with Kawasaki syndrome, who, due to jaundice, enlarged liver and abnormal liver function tests, was admitted the hospital with the suspicion of liver disease. The symptoms of Kawasaki syndrome appeared during the first nine days of the hospital stay. The authors emphasise, that liver function tests are frequently abnormal in adults presenting with this clinical entity, therefore Kawasaki syndrome should be taken into consideration in the differential diagnosis of liver diseases.


Subject(s)
Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Adolescent , Adult , Age of Onset , Diagnosis, Differential , Hepatomegaly/etiology , Humans , Jaundice/etiology , Liver Diseases/diagnosis , Liver Function Tests , Male , Mucocutaneous Lymph Node Syndrome/enzymology
12.
Br J Cancer ; 84(8): 1043-6, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11308251

ABSTRACT

A phase II programme was carried out in both Europe and North America to evaluate the activity of topotecan administered as a 21-day continuous intravenous infusion to patients with recurrent ovarian cancer. The European results are reported here. Patients who had failed first line therapy with a platinum-based regimen received topotecan 0.4 mg/m(2)/day, as a 21-day infusion every 28 days. Patients were only permitted one prior regimen. 35 patients were enrolled and evaluable for response. 3 patients (8.6%) had a partial response to treatment (95% CI 1.8%, 23.1%) with a median time to response of 8.1 weeks and a median duration of response of 17.6 weeks. Response was also evaluated by CA125 and was also found to be 8%. For all 35 patients, median time to progression was 16.1 weeks and median survival was 43.6 weeks. The principal toxicity was myelosuppression although grade 4 neutropenia occurred in only 8.8% of patients (2.1% of courses) and infectious complications were relatively infrequent. Non-haematological toxicity was generally mild and mainly consisted of gastrointestinal events, alopecia and fatigue. A prolonged infusion of topotecan was well tolerated with a low incidence of severe neutropenia. Responses were seen in both North American and European patients. Response rates varied between the 2 studies possibly due to differences in patient demographics.


Subject(s)
Antineoplastic Agents/therapeutic use , Ovarian Neoplasms/drug therapy , Topotecan/therapeutic use , Abdominal Pain/chemically induced , Adult , Aged , Alopecia/chemically induced , Antineoplastic Agents/adverse effects , Diarrhea/chemically induced , Fatigue/chemically induced , Female , Hematologic Diseases/chemically induced , Humans , Infusions, Intravenous , Middle Aged , Nausea/chemically induced , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Survival Analysis , Survival Rate , Time Factors , Topotecan/adverse effects , Treatment Outcome , Vomiting/chemically induced
13.
Br J Cancer ; 84 Suppl 1: 11-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11308269

ABSTRACT

Anaemia is a common occurrence in patients with cancer, and currently can be treated in several ways. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa) was created using site-directed mutagenesis to have 8 more sialic acid side chains than recombinant human erythropoietin (rHuEPO). The additional sialic acid content has resulted in an approximately 3-fold greater half-life relative to rHuEPO in patients with chronic renal failure. This study evaluates the pharmacokinetic profile of NESP in patients receiving multiple cycles of chemotherapy. Anaemic patients (haemoglobin < or = 11.0 g dl(-1)) who had non-myeloid malignancies received NESP weekly (2.25 mcg kg(-1) wk(-1)) under the supervision of a physician, starting on day 1 of chemotherapy for 3 chemotherapy cycles given at 3-week intervals. Blood samples were collected during chemotherapy cycles 1 and 3 for pharmacokinetic analysis. All patients were followed for 4 weeks after treatment. NESP was well tolerated by all patients. After a single dose during chemotherapy cycle 1, pharmacokinetic parameters (mean (SD), n) for the first 15 patients were: T(max)86.1 (22.8) h (n = 14); C(max)9.0 (5.1) ng ml(-1)(n = 14); t(1/2,z)32.6 (11.8) h (n = 7); CL/F 3.7 (1.0) ml h(-1) kg(-1)(n = 7). The subjects for whom all parameters could be calculated may represent a sub-group of the entire population. Similar results were obtained in cycle 3. In addition, haemoglobin response data suggests that, in this patient population, dosing less frequently than the 3 times weekly doses used for rHuEPO may be possible while improving anaemia.


Subject(s)
Anemia/drug therapy , Erythropoietin/pharmacokinetics , Neoplasms/complications , Adult , Aged , Anemia/etiology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Darbepoetin alfa , Drug Administration Schedule , Drug Interactions , Erythropoiesis/drug effects , Erythropoietin/administration & dosage , Erythropoietin/analogs & derivatives , Erythropoietin/blood , Erythropoietin/chemistry , Erythropoietin/therapeutic use , Female , Half-Life , Hemoglobins/analysis , Humans , Injections, Subcutaneous , Male , Middle Aged , N-Acetylneuraminic Acid/chemistry , Neoplasms/drug therapy , Recombinant Proteins/administration & dosage , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use , Safety
14.
Proc Natl Acad Sci U S A ; 97(25): 13732-7, 2000 Dec 05.
Article in English | MEDLINE | ID: mdl-11095729

ABSTRACT

The split-ubiquitin assay detects protein interactions in vivo. To identify proteins interacting with Gal4p and Tup1p, two transcriptional regulators, we converted the split-ubiquitin assay into a generally applicable screen for binding partners of specific proteins in vivo. A library of genomic Saccharomyces cerevisiae DNA fragments fused to the N-terminal half of ubiquitin was constructed and transformed into yeast strains carrying either Gal4p or Tup1p as a bait. Both proteins were C-terminally extended by the C-terminal half of ubiquitin followed by a modified Ura3p with an arginine in position 1, a destabilizing residue in the N-end rule pathway. The bait fusion protein alone is stable and enzymatically active. However, upon interaction with its prey, a native-like ubiquitin is reconstituted. RUra3p is then cleaved off by the ubiquitin-specific proteases and rapidly degraded by the N-end rule pathway. In both screens, Nhp6B was identified as a protein in close proximity to Gal4p as well as to Tup1p. Direct interaction between either protein and Nhp6B was confirmed by coprecipitation assays. Genetic analysis revealed that Nhp6B, a member of the HMG1 family of DNA-binding proteins, can influence transcriptional activation as well as repression at a specific locus in the chromosome of the yeast S. cerevisiae.


Subject(s)
DNA-Binding Proteins/physiology , Fungal Proteins/genetics , Fungal Proteins/physiology , Nuclear Proteins/physiology , Promoter Regions, Genetic , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/genetics , Transcription Factors/genetics , Base Sequence , DNA Primers , Fungal Proteins/metabolism , HMGN Proteins , Protein Binding
15.
Z Gastroenterol ; 38(10): 821-5, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11089265

ABSTRACT

OBJECTIVES: Little is known about the fungal colonization of the esophagus. Since alcoholic liver disease (ALD) patients are prone to fungal esophagitis, we have investigated the esophageal fungal colonization of this patient group. METHODS: One hundred consecutive ALD patients were enrolled in this prospective study. 22 patients with dyspeptic symptoms acted as controls. After taking an oropharyngeal swab, patients underwent an upper gastrointestinal endoscopy and surface material was obtained from the esophagus for direct smears and culture. RESULTS: In the ALD group pseudohyphae were found in 21.5% and yeast forms in 6.4% of the direct smears. The culture was positive in 40.8% of the ALD patients, the isolated strains were: 30 C. albicans, 2 C. kefyr, 2 C. krusei, 1 C. zeylanoides and in 3 cases the species could not be identified. 41.9% of ALD patients and 13.6% of control patients (p = 0.013) had fungi in their esophagus. Significantly more ALD patients had fungal esophagitis than in the control group (19.3% vs. 0%, p = 0.021), the rate of fungal colonization was also higher, but the difference was not significant (22.5% vs. 13.6%). A significantly higher rate of fungal esophagitis and esophageal colonization was found in patients with fungi in their oropharyngeal swabs (p = 0.00001). CONCLUSIONS: Fungal colonization of the esophagus is frequent in ALD patients. Its presence might have clinical significance in the case of liver transplantation.


Subject(s)
Candida/isolation & purification , Esophagus/microbiology , Geotrichum/isolation & purification , Liver Diseases, Alcoholic/microbiology , Adult , Aged , Chi-Square Distribution , Endoscopy, Gastrointestinal , Esophagitis/microbiology , Female , Humans , Male , Middle Aged , Oropharynx/microbiology , Prospective Studies
16.
Neuroscience ; 96(1): 51-8, 2000.
Article in English | MEDLINE | ID: mdl-10683409

ABSTRACT

Although the long-term neurobiological and behavioral effects of nigrostriatal lesions are well characterized, the events occurring soon after injury are not. These acute events can provide insight into the mechanisms underlying long-term adaptations to nigrostriatal lesions. The present experiments examined the basal ganglia immediate-early gene response to infusions of the catecholamine neurotoxin 6-hydroxydopamine into the nigrostriatal pathway in rats. Following 6-hydroxydopamine infusions into the medial forebrain bundle in awake, behaving rats, there was a rapid and transient induction of striatal c-fos and zif/268 messenger RNAs. Both immediate-early genes were maximally induced by 45min post-infusion, and returned to control levels by 1.5h (c-fos) or 3h (zif/268) post-infusion. Double-labeling experiments revealed that striatal c-fos expression occurred preferentially in preproenkephalin-expressing neurons. 6-Hydroxydopamine-induced c-fos messenger RNA was also observed in the substantia nigra pars reticulata and entopeduncular nucleus, but not the globus pallidus, 45 min after medial forebrain bundle 6-hydroxydopamine infusions. Finally, the role of ionotropic striatal glutamate receptors in nigrostriatal injury-induced striatal c-fos was examined by combining medial forebrain bundle 6-hydroxydopamine infusions with intrastriatal glutamate antagonist infusions. Both the N-methyl-D-aspartate antagonist, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and the non-N-methyl-D-aspartate antagonist, 6,7-dinitroquinoxaline-2, 3-dione, blocked striatal induction of c-fos messenger RNA following 6-hydroxydopamine infusions into the medial forebrain bundle. These results provide evidence of rapidly developing, glutamate-dependent molecular responses in the basal ganglia which may contribute to some of the well-described long-term adaptations of this system to nigrostriatal injury.


Subject(s)
Gene Expression , Genes, Immediate-Early/genetics , Medial Forebrain Bundle/drug effects , Medial Forebrain Bundle/physiopathology , Oxidopamine/pharmacology , Animals , Basal Ganglia/metabolism , Behavior, Animal , Excitatory Amino Acid Antagonists/pharmacology , Male , Medial Forebrain Bundle/pathology , Motor Activity , Piperazines/pharmacology , Quinoxalines/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Sensation , Time Factors
17.
Cancer Chemother Pharmacol ; 45(4): 291-7, 2000.
Article in English | MEDLINE | ID: mdl-10755317

ABSTRACT

PURPOSE: [corrected] Capecitabine (Xeloda) is a novel fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumors. The purpose of this study was to demonstrate the preferential activation of capecitabine, after oral administration, in tumor in colorectal cancer patients, by the comparison of 5-FU concentrations in tumor tissues, healthy tissues and plasma. METHODS: Nineteen patients requiring surgical resection of primary tumor and/or liver metastases received 1,255 mg/m2 of capecitabine twice daily p.o. for 5-7 days prior to surgery. On the day of surgery, samples of tumor tissue, adjacent healthy tissue and blood samples were collected simultaneously from each patient, 2 to 12 h after the last dose of capecitabine had been administered. Concentrations of 5-FU in various tissues and plasma were determined by HPLC. The activities of the enzymes (CD, TP and DPD) involved in the formation and catabolism of 5-FU were measured in tissue homogenates, by catabolic assays. RESULTS: The ratio of 5-FU concentrations in tumor to adjacent healthy tissue (T/H) was used as the primary marker for the preferential activation of capecitabine in tumor. In primary colorectal tumors, the concentration of 5-FU was on average 3.2 times higher than in adjacent healthy tissue (P = 0.002). The mean liver metastasis/healthy tissue 5-FU concentration ratio was 1.4 (P = 0.49, not statistically different). The mean tissue/plasma 5-FU concentration ratios exceeded 20 for colorectal tumor and ranged from 8 to 10 for other tissues. CONCLUSIONS: The results demonstrated the preferential activation of capecitabine to 5-FU in colorectal tumor, after oral administration to patients. This is explained to a great extent by the activity of TP in colorectal tumor tissue, (the enzyme responsible for the conversion of 5'-DFUR to 5-FU), which is approximately four times that in adjacent healthy tissue. In the liver, TP activity is approximately equal in metastatic and healthy tissue, which explains the lack of preferential activation of capecitabine in these tissues.


Subject(s)
Antimetabolites, Antineoplastic/metabolism , Colorectal Neoplasms/metabolism , Deoxycytidine/analogs & derivatives , Fluorouracil/metabolism , Prodrugs/metabolism , Aged , Biotransformation , Capecitabine , Chromatography, High Pressure Liquid , Colon/metabolism , Cytidine Deaminase/metabolism , Deoxycytidine/metabolism , Dihydrouracil Dehydrogenase (NADP) , Female , Humans , Liver/metabolism , Male , Middle Aged , Oxidoreductases/metabolism , Rectum/metabolism , Spectrophotometry, Ultraviolet , Thymidine Phosphorylase/metabolism
18.
Clin Cancer Res ; 5(7): 1696-702, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10430071

ABSTRACT

Capecitabine (Xeloda) is a rationally designed oral, tumor-selective fluoropyrimidine carbamate aimed at preferential conversion to 5-fluorouracil (5-FU) within the tumor. Because capecitabine is extensively metabolized by the liver, it is important to establish whether liver dysfunction altered the pharmacokinetics of capecitabine and its metabolites. This was investigated in 14 cancer patients with normal liver function and in 13 with mild to moderate disturbance of liver biochemistry due to liver metastases. They received a single oral dose of capecitabine (1255 mg capecitabine/m2) with serial blood and urine samples collected up to 72 h after administration. Concentrations of capecitabine and its metabolites were determined in plasma by high-performance liquid chromatography or liquid chromatography coupled to mass spectrometry and in urine by 19F-nuclear magnetic resonance spectroscopy. Although plasma concentrations of capecitabine, 5'-deoxy-5-fluorouridine, 5-FU, dihydro-5-FU, and alpha-fluoro-beta-alanine were, in general, higher in patients with liver dysfunction, the opposite was found for 5'-deoxy-5-fluorocytidine. These effects were not clinically significant. Total urinary recovery of capecitabine and its metabolites was 71% of the administered dose in patients with normal hepatic function and 77% in patients with hepatic impairment. The absolute bioavailability of 5'-deoxy-5-fluorouridine was estimated as 42% in patients with normal hepatic function and 62% in patients with impaired hepatic function. In summary, mild to moderate hepatic dysfunction had no clinically significant influence on the pharmacokinetic parameters of capecitabine and its metabolites. Although caution should be exercised when capecitabine is administered to patients with mildly to moderately impaired hepatic function, there is no need for, a priori, adjustment of the dose.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Deoxycytidine/analogs & derivatives , Liver Diseases/metabolism , Liver Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Capecitabine , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Deoxycytidine/adverse effects , Deoxycytidine/metabolism , Deoxycytidine/pharmacokinetics , Female , Fluorouracil/analogs & derivatives , Humans , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Metastasis
19.
Brain Res Mol Brain Res ; 69(1): 149-53, 1999 May 21.
Article in English | MEDLINE | ID: mdl-10350647

ABSTRACT

The present study examines dopaminergic regulation of neuropeptide gene expression within a relatively poorly characterized population of cells, the preproenkephalin (PPE) mRNA containing neurons of the globus pallidus (GP). Rats that received 6-hydroxydopamine (6-OHDA) lesions or repeated D1 or D2 antagonist administration were compared to control animals. One month after 6-OHDA lesions, PPE mRNA was elevated in the GP ipsilateral to the lesion, with a smaller elevation also being observed in the contralateral GP. Repeated administration of eticlopride, but not SCH 23390, also resulted in elevated PPE mRNA expression in the GP. These data reveal a novel effect of decreased dopamine transmission on the GP, and draw attention to this subpopulation of pallidal neurons.


Subject(s)
Dopamine/physiology , Enkephalins/genetics , Globus Pallidus/chemistry , Globus Pallidus/physiology , Protein Precursors/genetics , Animals , Benzazepines/pharmacology , Dopamine Antagonists/pharmacology , Gene Expression/drug effects , Gene Expression/physiology , Globus Pallidus/cytology , Male , Neurons/chemistry , Neurons/drug effects , Neurons/physiology , Oxidopamine , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Salicylamides/pharmacology , Substantia Nigra/chemistry , Substantia Nigra/cytology , Substantia Nigra/physiology , Sulfur Radioisotopes , Sympatholytics
20.
Med Klin (Munich) ; 94(12): 695-8, 1999 Dec 15.
Article in German | MEDLINE | ID: mdl-10641513

ABSTRACT

BACKGROUND: The emphysematous pyelonephritis is a life-threatening complication of a bacterial interstitial nephritis, and it occurs mainly in diabetics. The infection with optional anaerobic microorganisms, which are able to produce gas, is supported by a reduced state of resistance, a high glucose level in the tissue in diabetic derailment and ischemia in the infected organ, for example by a kidney infarction or by an obstructive uropathy. Mostly the inflammation occurs unilateral, only in 10% of all cases both kidneys are affected. Computer tomography allows a fast diagnosis by demonstrating gas accumulation in the kidney. Surgical measures and antibiotic therapy are the principal therapeutic methods. CASE REPORT: The example of a 55-year-old diabetic man with bilateral emphysematous pyelonephritis demonstrates the diagnostic and therapeutic possibilities. After a fast diagnostic procedure, immediate hemodialysis in uremia and bilateral nephrectomy let the patient survive in a stable clinical condition dependent on regular dialysis treatment.


Subject(s)
Acute Kidney Injury/microbiology , Escherichia coli Infections/complications , Escherichia coli Infections/diagnosis , Nephritis, Interstitial/complications , Nephritis, Interstitial/diagnosis , Acute Kidney Injury/therapy , Diabetes Mellitus, Type 1/complications , Diagnosis, Differential , Escherichia coli/isolation & purification , Escherichia coli Infections/therapy , Humans , Male , Middle Aged , Nephritis, Interstitial/microbiology , Nephritis, Interstitial/therapy
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