RCAT reflects symptom control and quality of life in allergic rhinoconjunctivitis patients.

BACKGROUND: The Global Allergy and Asthma European Network (GA2 LEN) Taskforce has requested more data on correlations between various patient-reported outcomes (PROs) in clinical trials on allergy. We compared three tools-the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Rhinitis Total Symptom Score (RTSS)-to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis. METHODS: In two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated. RESULTS: Upon comparing RCAT and RQLQ results, we found strong correlations of r = -0.871 for grass pollen-allergic patients and r = -0.795 for birch pollen-allergic patients. The comparison between RCAT and RTSS results showed a strong correlation of r = -0.811 (grass pollen-allergic patients) and a moderate correlation of r = -0.539 (birch pollen-allergic patients). In the RCAT, 69.7% of grass pollen-allergic patients and 45.7% of birch pollen-allergic patients receiving guideline-concordant therapy were regarded as having insufficiently controlled symptoms. CONCLUSION: The strong correlations suggest that the RCAT alone is equivalent to the RQLQ with respect to patients' symptom control and quality of life. Patients with uncontrolled symptoms can be identified using the RCAT. Hence, the physician can decide whether symptomatic therapy can be intensified or allergy immunotherapy should be administered.

LSD1 inhibition suppresses ASCL1 and de-represses YAP1 to drive potent activity against neuroendocrine prostate cancer.

Lysine-specific demethylase 1 (LSD1 or KDM1A ) has emerged as a critical mediator of tumor progression in metastatic castration-resistant prostate cancer (mCRPC). Among mCRPC subtypes, neuroendocrine prostate cancer (NEPC) is an exceptionally aggressive variant driven by lineage plasticity, an adaptive resistance mechanism to androgen receptor axis-targeted therapies. Our study shows that LSD1 expression is elevated in NEPC and associated with unfavorable clinical outcomes. Using genetic approaches, we validated the on-target effects of LSD1 inhibition across various models. We investigated the therapeutic potential of bomedemstat, an orally bioavailable, irreversible LSD1 inhibitor with low nanomolar potency. Our findings demonstrate potent antitumor activity against CRPC models, including tumor regressions in NEPC patient-derived xenografts. Mechanistically, our study uncovers that LSD1 inhibition suppresses the neuronal transcriptional program by downregulating ASCL1 through disrupting LSD1:INSM1 interactions and de-repressing YAP1 silencing. Our data support the clinical development of LSD1 inhibitors for treating CRPC - especially the aggressive NE phenotype. Statement of Significance: Neuroendocrine prostate cancer presents a clinical challenge due to the lack of effective treatments. Our research demonstrates that bomedemstat, a potent and selective LSD1 inhibitor, effectively combats neuroendocrine prostate cancer by downregulating the ASCL1- dependent NE transcriptional program and re-expressing YAP1.

Establishment of a continuous cell line from a human carcinoid of the small intestine (KRJ-I).

A new continuous cell line from a human malignant carcinoid of the small intestine (KRJ-I) was established. The cells showed morphological and immunocytochemical features of the tumor of origin and expressed estrogen receptors. The cells are growing as a suspension, forming multicellular aggregates and spheroids. Electron microscopy confirmed the presence of neuroendocrine granules. Dose-dependent growth inhibition was observed after incubation with 5-azacytidine. Cytogenetic analyses of the tumor of origin, the cell line KRJ-I and a liver metastasis KRJ-II revealed clonal tetraploidy and clonal loss of the Y-chromosome and chromosome 19.

Quinine versus carbamoylated quinine-based chiral anion exchangers. A comparison regarding enantioselectivity for N-protected amino acids and other chiral acids.

First, a chiral stationary phase was prepared by immobilization of the naturally occurring alkaloid quinine onto a 3-mercaptopropyl-modified silica gel via a radical addition reaction and it was evaluated for direct HPLC enantioseparation of acidic chiral compounds under buffered hydro-organic mobile phase conditions. Second, its enantioselectivity and retention characteristics for a representative set of N-derivatized alpha-amino acids and other chiral acids were compared with those of a similar weak chiral anion exchanger based on tert.-butyl carbamoylated quinine derivative as chiral selector. The results clearly indicate that the introduction of the carbamoyl functionality at the secondary hydroxyl group at C9 of quinine provides new and additional sites for intermolecular interactions with chiral analytes and this can profoundly change and improve chiral recognition ability, especially for amide, carbamate and sulfonamide derivatives of amino acids including DNB, Bz, Ac, For, Z, Fmoc, Boc and DNS-protected amino acids. The impact of this new and rigid hydrogen donor-acceptor group--directing stereoselective selector-selectand complexation by intermolecular hydrogen bonding--in comparison to the plain quinine selector is further evaluated by alkylation of the nitrogen atom of either the selector carbamate and/or of the amino function of leucine (N-methyl leucine) derivatized either by DNB or DNP groups.

Device for quenching studies on rare gas and metal halide excited complexes.

A device is described in which HgCl * is photolytically produced by optically exciting HgCl(2). The same apparatus can be used to excite other metal and rare gas complexes. The device is small, allowing rapid screening using repetitive pulsing and signal averaging techniques.

A CEO roundtable on making mergers succeed.

The announcement in January of the merger between America Online and Time Warner marked the convergence of the two most important business trends of the last five years--the rise of the Internet and the resurgence of mergers and acquisitions. M&A activity is at a fever pitch, spurred in large part by the breathtaking influx of capital into the Internet space. And all signs indicate the trend will only accelerate. Against this background, an impressive group of experienced deal makers came together to share their experiences of what makes mergers work. They were assembled in Scottsdale, Arizona, under the auspices of the M&A Group, a professional society formed in 1999 for CEOs interested in M&A as a business strategy. Participants included top executives from Internet start-ups like Teligent; venture capital firms like Baroda Ventures; financial institutions like Merrill Lynch and PricewaterhouseCoopers; and major corporations like Allstate, Tyco International, SmithKline Beecham, Rohm and Haas, VF, Crown Cork & Seal, and Hughes Space and Communications. The spirited and surprisingly frank discussion cut a wide swath, considering issues such as whether most mergers fail to pan out as well as expected, how to increase the odds of success, the nuts and bolts of the integration process, the trade-offs between acquiring a company and growing from within, the importance of cultural issues, and why anyone would want to be on the board of a merged company.

KrF laser-pumped dye-laser studies.

Dye-laser efficiency measurements were performed on four Coumarin dyes: C-485, C-498, C-500, and C-503, all operating near 500 nm. They were pumped with a 16-ns pulse-length KrF laser. The most efficient of the Coumarin dyes tested was C-498. The intrinsic efficiency of this dye was found to increase with pump rate. At a pump rate of 2 MW/cm(2), an intrinsic efficiency of > 20% was measured. Longer KrF laser pulses (> 1.2 µs) were also used to pump C-498 and resulted in comparable laser efficiencies at similar pump rates. The temporal relationship between the input KrF laser pump pulse and the output dye-laser pulse was studied and was found to differ significantly for long and short pulses. Significant improvement in long-pulse laser performance was observed when the laser-cavity configuration incorporated a skip mode.

[Eye diseases and ophthalmological care in a developing country (author's transl)]. / Augenkrankheiten und ophthalmologische Versorgung in einem Entwicklungsland. Bericht über ein Eye-Camp in Andhra Pradesh/Indien.

Five million blind people in India suffer from cataract, which is a curable condition. Untreated cataract accounts for more than half of the cases of blindness in that country. Twenty percent of all cases of blindness are caused by infections, while malnutrition accounts for 27% in children. In India, ophthalmological care has been provided for many years now in eye-camps. In cataract surgery, the expression method is customary. Trachomas at all stages, infectious eye diseases, traumatic lesions, vitamin A deficiency and leprosy are also diagnosed and treated in large numbers of cases. By way of an example the authors, assistants at the First Eye Clinic of Vienna University, describe an eye-camp in Andhra Pradesh where they worked. Work of this kind can be recommended to others.

[Follow-up study of macular function after retinal detachment surgery (author's transl)]. / Langzeitbeobachtungen der Makulafunktion nach geheilter Netzhautabhebung.

Forty patients successfully operated on for retinal detachment involving the macula were followed up for periods ranging from six months to nine years. The follow-up examination included testing for visual acuity, color perception and metamorphopsias, as well as biomicroscopy and fluorescein angiography. Postoperative visual acuity was correlated with the preoperative duration of retinal detachment. As expected, visual outcome was reduced in cases with lesions demonstrated by biomicroscopy and/or fluorescein angiography. In some patients visual acuity and color perception were impaired and metamorphopsias were present, even though the macula appeared normal in funduscopy and fluorescein angiography. This may be due to a possible misalignement of the photoreceptors as demonstrated in the owl monkey by Machemer.

Biologic and cytogenetic characterization of three human medullary thyroid carcinomas in culture.

Neuroendocrine features and cytogenetic abnormalities of one continuous cell line (MTC-SK) and two long-term cultures (GER, STAH) derived from three sporadic cases of human medullary thyroid carcinomas (MTCs) were studied. Specific neuroendocrine markers (NSE, chromogranins, calcitonin, calcitonin gene-related peptide) were identified by electron microscopy and immunocytochemistry. In situ hybridochemistry and Northern blot analysis confirmed endocrine activity. Cytogenetic studies of the cell line MTC-SK revealed three consistent marker chromosomes, t(3;10), 11p+, and 22p+. Cells of long-term cultures GER and STAH exhibited a consistent translocation t(2;18), a trisomy 7, and two consistent marker chromosomes der3 and 5p+, respectively. Recently, we have isolated 12 stable clones of this MTC-SK cell line, which showed two different growth patterns. Quantitative measurement of mitotic activity flow cytometry and semiquantitative analysis of AgNOR-, Ki67-, and Cyclin/PCNA-(immuno)reactivity showed different DNA composition and duplication rates, indicating at least two subpopulations. Some of our clones developed a new consistent marker (i.e., an unbalanced translocation between mar11p+ and 1q). However, no correlations between chromosome findings, growth rate, and neuroendocrine markers were observed.

[Electronic data processing-assisted high dosage therapy with stem cell transplantation at the Donauspital]. / EDV-unterstützte Organisation der Hochdosistherapie mit Stammzelltransplantation im Donauspital.

Organization of high dose chemotherapy with stem cell transplantation essentially requires EDV-support. "ONCOBASE" has been adapted into the Donauspital network on May 1, 1992. We report about the 2-year clinical experience with ONCOBASE: 1. ONCOBASE effectively supports communication between the ward, ambulance and hospital pharmacy (where all cytostatics are prepared). 2. ONCOBASE provides better surveillance concerning all therapeutic procedures including cytostatic drugs and supportive therapies. 3. ONCOBASE allows the generation of medical letters which include all drugs and supportive therapies delivered. 4. Since ONCOBASE is a database program, all informations concerning the patients are registered. These include cumulative drug doses, information on side effects, blood cell kinetics after previous therapies, kinetics of tumor markers and results of further examinations. 5. ONCOBASE permits rapid data exchange with other hospital networks using the communication data record governed by the "Arbeitskreis für EDV der deutschen Gesellschaft für Hämatoonkologie".