Biomedical subjects

J Toth

Publications and source records attributed to J Toth.

At least 37 records · Page 2Linked to original sources

PubMed1999

The influence of female sex hormones on nasal reactivity in seasonal allergic rhinitis.

BACKGROUND: This study aimed to investigate whether the hormone peaks of estrogen and progesterone could influence the extent of the allergic reaction in grass-pollen-allergic women. METHODS: Twenty-three allergic women with seasonal allergic rhinitis due to grass pollen were included in this trial. Twelve were taking oral contraceptives (OC) (control group), and 11 were taking no pill (target group). The subjects were challenged with grass pollen by nasal provocation test around day 14 of their menstrual cycle (ovulation day) and again at the end of the cycle (day 27). The primary criteria were the subjective nasal symptoms rhinorrhea, nasal blockage, itching, and sneezing. A further criterion was the objectively measured nasal mucosal swelling, assessed by active anterior rhinomanometry. All criteria were evaluated before and 15 min after provocation, and the hormone status was determined on each investigation day. RESULTS: Comparisons of symptoms between the groups resulted in P values of > 0.05 for all symptoms at both visits except the symptom blocked nose, which was significantly lower (P=0.03) in the patients with OC intake at visit 2, and the symptom sneezing, which showed a significantly (P=0.02) higher increase in patients taking OC at the end of the cycle. The flow decrease reached a greater extent in the target group than in the controls. CONCLUSIONS: These results indicate a correlation of the hormonal situation and the nasal allergic reactivity. OC intake led to an intensifying of neurogenic symptoms near the end of pill intake, a result which could be due to a protective effect of the endogenous progesterone, in contrast to the orally administered hormones.

Adult↗

PubMed1999

The ald gene, encoding a coenzyme A-acylating aldehyde dehydrogenase, distinguishes Clostridium beijerinckii and two other solvent-producing clostridia from Clostridium acetobutylicum.

The coenzyme A (CoA)-acylating aldehyde dehydrogenase (ALDH) catalyzes a key reaction in the acetone- and butanol (solvent)-producing clostridia. It reduces acetyl-CoA and butyryl-CoA to the corresponding aldehydes, which are then reduced by alcohol dehydrogenase (ADH) to form ethanol and 1-butanol. The ALDH of Clostridium beijerinckii NRRL B593 was purified. It had no ADH activity, was NAD(H) specific, and was more active with butyraldehyde than with acetaldehyde. The N-terminal amino acid sequence of the purified ALDH was determined. The open reading frame preceding the ctfA gene (encoding a subunit of the solvent-forming CoA transferase) of C. beijerinckii NRRL B593 was identified as the structural gene (ald) for the ALDH. The ald gene encodes a polypeptide of 468 amino acid residues with a calculated M(r) of 51, 353. The position of the ald gene in C. beijerinckii NRRL B593 corresponded to that of the aad/adhE gene (encoding an aldehyde-alcohol dehydrogenase) of Clostridium acetobutylicum ATCC 824 and DSM 792. In Southern analyses, a probe derived from the C. acetobutylicum aad/adhE gene did not hybridize to restriction fragments of the genomic DNAs of C. beijerinckii and two other species of solvent-producing clostridia. In contrast, a probe derived from the C. beijerinckii ald gene hybridized to restriction fragments of the genomic DNA of three solvent-producing species but not to those of C. acetobutylicum, indicating a key difference among the solvent-producing clostridia. The amino acid sequence of the ALDH of C. beijerinckii NRRL B593 was most similar (41% identity) to those of the eutE gene products (CoA-acylating ALDHs) of Salmonella typhimurium and Escherichia coli, whereas it was about 26% identical to the ALDH domain of the aldehyde-alcohol dehydrogenases of C. acetobutylicum, E. coli, Lactococcus lactis, and amitochondriate protozoa. The predicted secondary structure of the C. beijerinckii ALDH suggests the presence of an atypical Rossmann fold for NAD(+) binding. A comparison of the proposed catalytic pockets of the CoA-dependent and CoA-independent ALDHs identified 6 amino acids that may contribute to interaction with CoA.

Aldehyde Oxidoreductases↗

PubMed1999

Vinorelbine and carboplatin in recurrent and/or metastatic squamous cell carcinoma of the head and neck.

A phase II trial was performed to assess the safety and efficacy of the semisynthetic vinca alkaloid vinorelbine (VNR) when combined with carboplatin in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Treatment consisted of VNR 30 mg/m2 in 250 ml saline, infused over 30 min on days 1 + 8, and carboplatin 300 mg/m2 in 1,000 ml saline, infused over 2 h on day 1. Treatment was continued in patients achieving objective response or stable disease for a total of 6 courses. 24 patients entered this trial, 12 of whom had received prior induction chemotherapy and radiation, 2 had palliative chemotherapy and 10 had only radiation and/or surgery. We observed 2 partial response (9.5%), stable disease in 6 patients (28.5%) and progressive disease in 13 (62%). The dose-limiting toxicity was myelosuppression with grade 3 or 4 leukocytopenia in 11 patients (46%). Thrombocytopenia was seen in only 2 patients. The most frequent nonhematological toxicity was an acute pain at the tumor site. None of the patients experienced neurological symptoms or chemically induced phlebitis. VNR combined with carboplatin does not appear to improve the therapeutic armentarium in recurrent squamous cell carcinoma of the head and neck.

Adult↗

PubMed1998

Rhinoresistometry versus rhinomanometry--an evaluation.

Allergic nasal hyperreactivity is a common problem and many patients suffer from daily symptoms. Rhinomanometry is so far the only well established clinical method for objective assessment of nasal patency, although several expressions of nasal patency have been reported. Universal standardisation was achieved in 1983 in Brussels by Clement et al. [1], but many specialists are looking for a system giving more information on the functional aspects of the nose. A new development arising from active anterior rhinomanometry is rhinoresistometry. We tested this equipment, which has been introduced with new software for calculation and graphic presentation. 24 adult volunteers with proven allergy to grass pollen were examined immediately after long-term challenge in the Vienna Challenge Chamber [3] and 15 minutes after decongestion by application of 5% ephedrine solution. The similarity and differences between rhinomanometry and rhinoresistometry, as well as the value of the additional parameters are pointed out. Our data indicate that rhinoresistometry is a rapid, reproducible and non-invasive technique, which gives extended information in comparison to classic rhinomanometry. The results correlate very well with the findings obtained by the standard method. This pilot study demonstrates the benefit of the new parameters.

Adult↗

PubMed1998

Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients.

This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).

Adult↗

PubMed1998

Environmental priming influences allergen-specific nasal reactivity.

BACKGROUND: Preceding mucosal response to one allergen leads to the priming of the nasal mucosal response to another allergen. This study aimed to determine whether environmental allergens, especially ubiquitous animal dander, can induce nasal priming. METHODS: We investigated 26 grass-pollen-allergic subjects with additional sensitization to other aeroallergens. We performed continuous allergen challenge for 2 h with 1500 Dactylis glomerata pollen/m3 in the Vienna challenge chamber. The nasal flow at 150 Pa was examined, and subjective scores were obtained every 15 min. Statistical analysis was calculated from the area under curve of nasal flow reduction by Student's t-test and the Mann-Whitney U-test. Alpha was 0.05. RESULTS: In subjects with positive cat-dander RAST (class of > or = 3), besides grass-pollen allergy, the specific nasal allergic reaction to Dactylis challenge was significantly pronounced (P < 0.01), and an earlier onset of reaction was evident. The same results were obtained with additional sensitization to dog dander (P < 0.05). Concomitant sensitization to mugwort also led to escalating symptoms (P < 0.05). CONCLUSIONS: These results indicate that a specific nasal allergic reaction is augmented by environmental priming caused by ubiquitous animal dander and possibly is influenced by the daily use of spices.

Adult↗

PubMed1998

Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion.

BACKGROUND: The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine (PSE) 120 mg relative to placebo in patients with nasal congestion. METHODS: Twenty-four patients with perennial rhinitis due to house-dust-mite (HDM) allergy were recruited in this crossover study. A treatment period of 1 week, in which cetirizine/PSE was administered twice daily, was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient. Immediately after the first dose of each medication (day 1), nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces, with the Vienna Challenge Chamber (VCC), to investigate onset of action of the preparation. A second challenge of 3-h duration, carried out at least 12 h after the final dose, was undertaken after 1 week (mean) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state. RESULTS: The oral formulation of cetirizine/PSE was significantly (P<0.001) superior to placebo in improving nasal obstruction during both challenges. The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo (P<0.02). In addition, subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores (P<0.01). Both medications were well tolerated, and no serious adverse events occurred during the study. CONCLUSIONS: In this study, cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo. No serious adverse events occurred, and both regimens were equally well tolerated.

Administration, Oral↗

PubMed1998

Dose-dependent protection by azelastine eye drops against pollen-induced allergic conjunctivitis. A double-blind, placebo-controlled study.

The efficacy and tolerability of azelastine (CAS 58581-89-8) eye drops at three different doses (0.025%, 0.05% and 0.1%) were investigated in a double-blind, randomized, placebo-controlled, crossover study in 24 subjects with a history of allergic conjunctivitis/rhinoconjunctivitis, who were challenged, out of season, by airbone allergen in the "Vienna Challenge Chamber" (VCC). Subjects received a single dose of azelastine eye drops 60 min before the start of a 4 h challenge in the VCC. Additional local challenge, mimicking a gust of wind, was administered 15 min before the end of the session. Each of the 4 study days was separated by a 2 week washout period. Azelastine eye drops showed a dose-dependent inhibition of the development of itching of the eyes. The effect was most pronounced 15 min after the additional local challenge. A maximal effect was achieved at a dose of 0.05%. Similar effects were observed on lacrimation. Azelastine eye drops also dose-dependently inhibited the degree of conjunctival redness, measured by digital imaging, and tended to reduce the low incidence of chemosis observed. Ranking of the results of all symptoms for each treatment group confirmed the optimal effect at a dose of 0.05%. Azelastine eye drops had no effect on nasal and bronchial symptoms or on measurements of airways function (FEV1). No adverse effects of the treatments were reported. The data support the use of 0.05% azelastine eye drops in the treatment of allergic conjunctivitis/rhinoconjunctivitis.

Adult↗

PubMed1997

Modifications in Classic Relationships Corresponding to Gas/Solid Physical Adsorption

Most of the classic gas/solid isotherm equations are inconsistent with the general rules of surface thermodynamics. The mean cause of this inconsistency is the fact that, according to the exact thermodynamic relationships, if any calculations or considerations are made, the excess amount adsorbed on the surface should be taken into account. On the contrary, the classic isotherm relationships are calculated with the absolute amount adsorbed, that is, they neglect the differences between the densities of the gas-phase and the adsorbed-phase. This neglection leads to contradictions, especially at high equilibrium pressures when the classic equations calculate the total adsorption capacity by extrapolation of the equilibrium pressure to infinity. However, under the critical temperature (Tc) this extrapolation is a physical nonsense and there are some conditions at which this extrapolation above Tc is also irreal. All these problems can be solved if the classic isotherm equations are transformed to modified forms including a new parameter chi, which assures in every respect the thermodynamic consistency (correctness).

Journal Article↗

PubMed1997

Theft behaviour and its consequences among kleptomaniacs and shoplifters--a comparative study.

This study is based on interviews with 37 persons fulfilling the DSM-IV criteria for kleptomania recruited through newspaper advertisements, and on 50 shoplifters interviewed directly after apprehension. Our hypothesis was that there are no absolute borders between 'pure' kleptomania according to DSM-IV and other forms of shoplifting. When asked about the latest case of shoplifting, one fifth of the shoplifters reported not having stolen the item for personal use and had later discarded it. A quarter of the kleptomaniacs reported ambivalence when asked if they needed the item in question. The degree of reported impulsivity and a feeling of not being oneself at the time of the theft was the same in the two groups. The two groups also estimated their degree of impulsivity, planning, thrill, relief, vengeance, need, pleasure on a Visual Analogue Scale (VAS) as well as the degree of psychiatric imbalance on the latest theft occasion. These estimates showed that there were no differences between the groups concerning the degree of planning, psychological imbalance and the need for the stolen item in question. The kleptomaniacs rated a feeling of inner tension before the theft higher than the shoplifters. The same was true concerning a feeling of relief during the theft and impulsivity. However, the shoplifters also rated high on all these items. Altogether, these findings support our hypothesis that many shoplifters, even if they do not fulfill all DSM criteria for kleptomania, may constitute a significant medical problem and should be offered support and treatment. Anti-depressants as well as the educational programmes developed by the Shoplifters Alternatives may be effective not only in cases of kleptomania but also for more unselected groups of non-professional shoplifters.

Adolescent↗

PubMed1997

Some Consequences of the Application of Incorrect Gas/Solid Adsorption Isotherm Equations

Adsorption Equilibrium Data Handbook (D. P. Valenzuela and A. L. Myers, Prentice-Hall, Englewood Cliffs, NJ, 1989) includes many data on single gas isotherms excellently described by the Toth and UNILAN equations. This paper proves that in spite of the good mathematical applicability, the forms of the two mentioned equations-from a thermodynamic standpoint-are incorrect. As a consequence, the correct specific surface areas of the adsorbents cannot be calculated. The Toth equation can be transformed to a correct relationship and from this modified form correct values of the specific surface areas and isosteric heats of adsorption can be calculated. This correct form does not violate the old principle of the dynamic equilibrium of physical adsorption.

Journal Article↗

PubMed1997

Immunophenotypic and functional characterization of human tonsillar mast cells.

Mast cells (MC) are proinflammatory immune cells residing in various organs. Tissue-specific heterogeneity of MC has been described. The aim of this study was to establish the phenotype and functional profile of human tonsillar mast cells (ToMC) and to compare ToMC with lung-, skin-, and uterus MC. Tonsillar tissue was obtained from 23 patients suffering from hyperplastic tonsils and dispersed by enzymatic digestion. With the use of a combined toluidine blue/immunofluorescence staining technique, isolated ToMC were found to react with monoclonal antibodies (mAb) to immunoglobulin E, CD9, CD43, CD44, CD46, CD54, CD55, and CD59, as well as mAb to stem cell factor (SCF) receptor (CD117/c-kit). ToMC were not recognized by mAb to other cytokine receptors or mAb to CD3, CD11b, CD14, CDw17, the skin MC marker CD88 (C5aR) or CD89 (Fc alphaR). Activation of ToMC by recombinant human (rh) SCF or anti-IgE resulted in histamine secretion, whereas no effects were seen with rhC5a, rh granulocyte-macrophage colony-stimulating factor, or rh interleukin-1 through -10. In summary, ToMC exhibit functional and phenotypic properties similar to lung- or uterus MC. Unlike skin MC, ToMC lack C5aR and are unresponsive to rhC5a.

Antigens, Surface↗

PubMed1997

Cultures of "Clostridium acetobutylicum" from various collections comprise Clostridium acetobutylicum, Clostridium beijerinckii, and two other distinct types based on DNA-DNA reassociation.

The best-known acetone-butanol (solvent)-producing bacterium is the Weizmann organism, Clostridium acetobutylicum, which was used for starch-based industrial fermentation. In the past two decades, cultures of "C. acetobutylicum" from various culture collections have included organisms that were isolated for sugar (molasses)-based industrial solvent production. Recent biochemical and genetic studies have revealed significant differences among some of these "C. acetobutylicum" strains. We used DNA-DNA reassociation to analyze 39 cultures of "C. acetobutylicum" and phenotypically similar organisms from major collections. The results of this study clearly identified four groups intergroup reassociation values of less than 30%. All of the intragroup values except the value for one strain were 68% or more, which supported species status for each group. The C. acetobutylicum group (with ATCC 824 as the type strain) consisted of 17 cultures and had average reassociation values of 10% with the other three groups. All strains of C. acetobutylicum produced riboflavin in milk, and the cultures were bright yellow, which is useful for differentiating this species from the other three groups. The Clostridium beijerinckii group (with VPI 5481 [= ATCC 25752] as the type strain) consisted of 16 cultures and included strains NCIMB 8052 and NCP 270. Strains NCP 262 and NRRL B643 constituted the third group, whereas strain N1-4 ("Clostridium saccharoperbutylacetonicum") and its derivative, strain N1-4081, formed the fourth group. At present, the last two groups are each represented by only one independent strain; definitive descriptions of these two groups as two new or revived species will require further phenotypic characterization, as well as identification of additional strains. C. beijerinckii NCP 270, Clostridium sp. strain NRRL B643, and "C. saccharoperbutylacetonicum" were used in industrial solvent production from molasses, which confirms that the new organisms used for the sugar-based processes are distinct from C. acetobutylicum.

1-Butanol↗

PubMed1997

Dynamic contrast-enhanced FMPSPGR of the pancreas: impact on diagnostic performance.

OBJECTIVE: The objective of this study was to evaluate the diagnostic impact of dynamic contrast-enhanced fast multiplanar spoiled gradient-recalled imaging (FMPSPGR) of the pancreas. MATERIALS AND METHODS: MR imaging examinations of the upper abdomen for 101 patients were evaluated retrospectively and compared with histologic and surgical results as well as imaging or laboratory and clinical follow-up results. Standard T1-weighted spin-echo images, T2-weighted fast spin-echo images with fat saturation, and FMPSPGR had been obtained for all patients. Of the 101 patients, 79 also underwent fat-saturated contrast-enhanced T1-weighted spin-echo MR imaging. Qualitative analysis consisted of evaluation of overall image quality and characterization of the pancreas as normal or abnormal, for which receiver operating characteristic curves were calculated. A contrast-to-noise ratio between the pancreas and the surrounding tissue was calculated for each patient. RESULTS: By a statistically significant margin, FMPSPGR performed better than conventional spin-echo MR imaging. For FMPSPGR, sensitivity and specificity were 87% and 100%, respectively, compared with T1-weighted spin-echo sequences (sensitivity, 50%; specificity, 96%), T2-weighted spin-echo sequences with fat saturation (sensitivity, 60%; specificity, 93%), and contrast-enhanced T1-weighted spin-echo sequences with fat saturation (sensitivity, 53%; specificity, 90%). Diagnostic confidence was highest with FMPSPGR. CONCLUSION: FMPSPGR should be used in all MR imaging examinations of the upper abdomen. This technique offers better visualization of important structures and increases confidence for a more specific and accurate diagnosis than does conventional spin-echo imaging.

Contrast Media↗

PubMed1996

Allele loss from large regions of chromosome 17 is common only in certain histological subtypes of ovarian carcinomas.

Using a panel of ten polymorphic markers, we examined the frequency of loss of heterozygosity (LOH) on chromosome 17 in 55 sporadic ovarian tumours. LOH on 17p and 17q was observed to be 50% and 62% respectively. LOH at D17S5 was detected in 24/36 (67%) of malignant cases and in 19/43 (44%) at TP53; the marker D17S855 intragenic to the BRCA1 gene showed allele loss in 50% (20/40) cases. The data presented here suggest that loss of the whole chromosome 17 is a relatively frequent event (30%) in ovarian carcinomas and this observation is especially frequent for serous, transitional cell and anaplastic histological subtypes. Mucinous and endometrioid ovarian tumours showed only short interstitial deletions (4/11, 36%). The overall frequency of the short deletions was relatively low (7/43, 16%) in our panel of carcinomas. Amplification of c-erbB-2/neu oncogene was detected in 32% (11/34) of the carcinomas tested; the gene was amplified only in those histological subtypes in which high incidence of LOH on chromosome 17 was observed, and was associated with advanced stages of the disease. We conclude that different histological types of tumour may have different aetiological mechanisms, and tumour-suppressor genes on chromosome 17 might be associated specifically with serous and transitional cell ovarian carcinomas.

Alleles↗

PubMed1996

Personality traits and psychiatric and somatic morbidity among kleptomaniacs.

Although the behaviour of kleptomania has been identified for decades, very little is known about the reasons, prevalence, course and treatment of this disorder. Current knowledge about kleptomania is generally derived from case reports or from material collected from highly selected groups. There are no published systematic studies of personality traits among kleptomaniacs, and knowledge of somatic and psychiatric co-morbidity is limited. The purpose of the present study was to describe personality characteristics, psychiatric disorders and somatic illness among kleptomaniacs. A total of 37 patients (two-thirds of whom were female) who fulfilled the DSM-IV criteria for kleptomania were recruited by advertising in a daily newspaper. Monotony avoidance was a prominent personality trait, as was a low degree of socialization. Depression and anxiety were also very common, as was a history of attempted suicide. Somatic illness was commonly reported, and a high proportion of the kleptomaniacs were regularly receiving pharmacological treatment for either psychiatric or somatic illness. The representativeness of this group of kleptomaniacs is as yet unknown. However, the present study is based on the largest sample of patients fulfilling DSM-III-R/DSM-IV criteria for kleptomania to date who were not primarily recruited through the medical or legislative systems.

Adolescent↗

PubMed1996

Efficacy and tolerability of astemizole-D and Loratadine-D during prolonged, controlled allergen challenge in the Vienna Challenge Chamber.

This randomized, double-blind, single-dummy, cross-over trial was initiated to compare the efficacy and tolerability of once-daily astemizole-D (CAS 141623-30-5; 10 mg astemizole/240 mg pseudoephedrine) with twice-daily loratadine D (CAS 132316-36-0; 5 mg loratadine/120 mg pseudoephedrine) during prolonged, controlled allergen challenge in the Vienna Challenge Chamber. Twelve atopic patients participated in this study with a treatment duration of 3 days. Pollen challenges were made on days 1 and 3: the first to assess onset of drug action; the second to determine duration of drug effect. Drug efficacy was assessed using a number of standard objective and subjective measures. Onset of action was found to be generally comparable in both treatment groups for all parameters tested with a mean overall onset of action of 65 min during treatment with astemizole-D compared with 70 min on loratadine-D. As expected, astemizole-D tended to have a longer duration of action, with symptom severity lower with this agent than with loratadine-D during the second challenge session despite the differences in dosing schedule. However, inter-group differences did not attain statistical significance. Patient evaluations of therapeutic efficacy confirm these findings. Both drugs were well-tolerated, although a non-significant trend towards greater sleep impairment was seen during treatment with loratadine-D. In conclusion, astemizole-D was shown to be at least as effective and well tolerated as loratadine-D for the treatment of allergen-induced rhinoconjunctivitis during prolonged, controlled allergen challenge.

Adult↗

PubMed1995

Efficacy of sulofenur and a second generation diarylsulfonylurea, N-[5-(2,3-dihydrobenzofuryl)sulfonyl]-N'-(3,4-dichlorophenyl)urea (LY295501), against colon adenocarcinoma xenografts.

Sulofenur and a second generation diarylsulfonylurea (DSU), N-[5-(2,3-dihydrobenzofuryl)sulfonyl]-N'-(3,4-dichlorophenyl)urea (LY295501), were evaluated against a panel of eight colon adenocarcinoma xenografts. Of these tumors, four were derived from adult patients and four from young patients (age range 11-26 years). Both drugs were administered twice daily by oral gavage, 5 days each week for two or three consecutive weeks. The maximum tolerated dose for sulofenur was 300 mg/kg/dose for three courses and 200 mg/kg/dose for LY295501. Against 'adult' derived tumors, sulofenur caused a high proportion of objective regressions of advanced xenografts in two of four lines, with significant inhibition of growth in three tumor lines. Colon adenocarcinomas from young patients were similarly sensitive to sulofenur with a high proportion of complete and partial responses in two of three lines. LY295501 demonstrated a very similar spectrum of activity against this panel of xenografts. Tumors intrinsically resistant to sulofenur were resistant to LY295501, although this agent was slightly more active than sulofenur against tumors from younger patients. In addition, xenografts were established from a cloned colon adenocarcinoma line (GC3/c1) and its derivative GC3/LYC5) selected in vitro for resistance to sulofenur. GC3/c1 xenografts were highly responsive to both sulofenur and LY295501, whereas GC3/LYC5 xenografts were completely resistant to both agents administered at the maximum tolerated dose and schedule. These results indicate that the second generation DSU, LY295501, demonstrates a similar spectrum of activity against colon tumors as does sulofenur, and that the mechanism of action and/or resistance to the two drugs is probably similar.

Adenocarcinoma↗