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M Worm

Publications and source records attributed to M Worm.

71 records · Page 4Linked to original sources
PubMed1993

Brain metastases of metastatic malignant melanoma: response to DTIC and interferon-gamma.

The prognosis of patients with malignant melanoma and brain metastases is poor. Therapy of brain metastases is difficult and mostly unsuccessful, with brain metastases being the predominant factor which determines overall survival. We report here on a patient whose brain metastases responded to DTIC + INF-gamma. We present a short summary on the different effects on INF-alpha and INF-gamma and reach the conclusion that clinical trials which combine DTIC and INF-gamma should be performed. Based on this observation, combinations including INF-alpha are not necessarily comparable to modalities which include INF-gamma.

Aged↗
PubMed1993

Responsiveness to interferon treatment of human melanoma cells correlates to immunophenotype.

Clinical trials with interferon (INF) treatment in patients with advanced metastatic melanoma have met with limited success, suggesting that only a small subgroup of patients with melanoma is sensitive to INF therapy. For therapeutic strategies, it would be of great value to discriminate and define markers related to the anti-proliferative effects of INF. In the present study, we report on the in vitro growth inhibitory effects of INF in six human melanoma cell lines; this is associated with a modulation of cell surface markers. The responsiveness of human melanoma cell lines in vitro to INF-alpha shows a good correlation with a specific immunophenotype (TA99-/EGF-R+ or HLA-DR+). No marker correlated with sensitivity or resistance to INF-beta or INF-gamma. This is the first report identifying cell surface markers of human melanoma cells which might have a predictive value for the clinical response to INF-alpha.

Antibodies, Monoclonal↗
PubMed1993

Amelanotic malignant melanoma presenting as malignant schwannoma.

A 78-year-old woman presented with a 14-month history of a nodule on the sole of her left foot. It had been increasing in size, and had become ulcerated. Histological, immunochemical and ultrastructural studies of the primary tumour revealed melanocytic and Schwannian characteristics, and posed diagnostic difficulties. The final diagnosis of a malignant melanoma with Schwannian differentiation was established on the basis of the clinical course, with the development of metastases in the subcutis, lymph nodes, liver and brain, as well as a shift in differentiation of the metastases towards cells containing giant melanosomes, typical of melanoma.

Aged↗
PubMed1993

Predominance of the major allergen (Alt a I) in Alternaria sensitized patients.

Thirty-nine patients sensitized to Alternaria were evaluated using titrated skin-prick test (SPT), histamine release studies (HR), inhibition of RAST and immunoblotting studies. To determine the relevance of the major allergen, Alt a I, specific rabbit antibodies against Alt a I and Alt a B were used. The antibodies were preincubated at different concentrations: (i) with the Alternaria allergen dose required for maximum response in the HR assay (10 BU/ml) and (ii) with the Alternaria antigen coupled to RAST paper discs (1000 BU/disc). Dose dependent inhibition of histamine release (n = 30, mean = 80% +/- 4%, IC30 = 0.69 micrograms/ml) and of RAST (n = 7, IC30 = 4.4 micrograms/ml) was found in all patients sensitized to Alternaria as indicated by allergen induced HR. The greater the response to Alternaria in HR, the higher the antibody concentrations necessary for inhibition (P < 0.05). Immunoblot experiments (n = 25) using SDS-PAGE showed in all cases IgE- and IgG binding at approximately 28 kD, which is the size reported for the major allergen, Alt a I. In two cases, slight IgE binding at 45 and 66 kD was also found, while in two other patients, only IgE binding at 66 kD was seen. Our findings emphasize the major importance of Alt a I in patients sensitized to Alternaria.

Adolescent↗
PubMed1993

Expression of growth factor receptors on human melanoma cells: comparison of modulating effects of interferons and retinoids.

Autocrine and paracrine growth factors are important mediators in malignant transformation. Interferons (IFN) and retinoids (RX) are well-known differentiative and immunomodulating agents with effects on subsets of different human tumors including malignant melanoma. In this study, we examined the modulating effects of three IFN and seven different RX on human melanoma cell lines regarding growth factor receptor expression. Growth factor receptor expression, including PDGF-R, NGF-R, EGF-R, IR, IGF-I-R, TFR and c-kit, was studied by immunohistochemistry and FACSscan analysis. Both groups of substances modulated the expression of some growth factor receptors. Upregulation of PDGF-R was seen after treatment with IFN as well as with RX. In contrast, EGF-R was found to be downregulated in two EGF-R-positive cell lines by IFN and, on the other hand, induced by RX in two EGF-R-negative cell lines. The expression of NGF-R was modulated ambiguously by these substances but demonstrated a cell line specificity in the different melanoma cell lines tested. Additionally, some of the tested growth factor receptors were not markedly changed regarding their expression by treatment with IFN and RX (IR, IGF-I-R, c-kit, TFR).

Adjuvants, Immunologic↗
PubMed1993

Preliminary evaluation of high-frequency chest compression for secretion clearance in mechanically ventilated patients.

BACKGROUND: A high-frequency chest compression (HFCC) device called the ThAIRapy System has been developed to provide secretion clearance therapy. We evaluated the safety, efficacy, and utility of the device in long-term mechanically ventilated patients. DESCRIPTION OF DEVICE: The primary components of the device are an air-pulse generator and an inflatable vest. Small gas volumes are alternately injected into and withdrawn from the vest by the air-pulse generator at a fast rate, creating an oscillatory or vibratory motion. The pulses cause the vest to inflate and deflate against the thorax of the patient. EVALUATION METHODS: We evaluated HFCC by comparing it to percussion and postural drainage therapy (P&PD); sputum production, patient comfort (PC), pulse-oximetry saturation (SpO2), heart rate (HR), and blood pressure (BP) data were collected and compared between the 2 methods. We monitored the reliability of the device and distributed a survey questionnaire to the entire respiratory therapy staff to assess utility. EVALUATION RESULTS: Nine patients completed the safety and efficacy portion of our evaluation. No significant difference was found between P&PD and HFCC in the wet weight of collected sputum, the mean change-in-percent of SpO2 or the mean percent change from baseline in HR, BP, or PC. All therapists believed that the ThAIRapy System was easy to learn, and 70% considered it an acceptable alternative to P&PD. Of the staff members surveyed, 80% believed that use of the HFCC device resulted in time savings in all or most cases. There were no equipment malfunctions in 225 hours of use. CONCLUSIONS: Compared to P&PD, HFCC via the ThAIRapy System may be equally efficacious in promoting secretion clearance in long-term mechanically ventilated patients. HFCC is neither more nor less safe for patients than is P&PD using SpO2, HR, BP, and PC as outcome variables. Most of our respiratory therapists perceived HFCC as an acceptable alternative to P&PD.

Data Collection↗
PubMed1987

[Unemployment in psychiatric patients].

Occupational activity was studied in a representative sample of 450 patients from 5 in- and out-patient psychiatric institutions: among the patients of working age 16.5% were unemployed, 11.9% received social relief, and 13.9% were on a premature retirement pension, i.e. all in all 42.3% had to give up occupational activity prematurely. Only 30.1% were gainfully employed. An analysis of the results according to diagnosis showed particularly schizophrenic patients to be at a disadvantage (highest rate of premature retirement pensioners, lowest rate of employers), as well as alcoholics (highest rate of unemployment). The occupational situation of neurotic and psychosomatic patients was affected in a less degree. The data were compared to those of the general population. Psychiatric patients, we had to confirm, are particularly at a disadvantage when unemployment is generally high. Another important factor, however, seems to be that patients, their families, doctors and employers estimate capacity of performance on account of the specific illness, thus calling for intensified efforts toward rehabilitation.

Adult↗
PubMed1982

(+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 1. Synthesis and evaluation of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and analogues as potential antidepressant agents.

A series of (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepines and (+/-)-4,5-dihydro-4-phenyl-1H-1,3-benzodiazepines was synthesized as part of a program to develop novel psychotropics. Of these compounds, (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (10a, HRP 543) emerged as a potential antidepressant. In in vivo mouse tests (inhibition of tetrabenazine-induced ptosis and potentiation of yohimbine toxicity) which are predictive of antidepressant-like activity, 10a is comparable to amitriptyline. The similarity is also maintained in vitro, as both 10a and amitriptyline inhibit norepinephrine and serotonin uptake into rat brain synaptosomes. No significant inhibition of rat brain monoamine oxidase A or B was found with 10a, nor did the compound potentiate tryptamine-induced seizures. On chronic administration, the number of cortical beta-adrenergic receptor sites was similarly reduced by 10a and desipramine. The anticholinergic activity of clinically useful antidepressants, such as amitriptyline, is a proposed cause of side effects which reduce patient compliance. In contrast to the tricyclics, 10a apparently lacks anticholinergic activity, as evidenced in vitro by negligible displacement of [3H]quinuclidinyl benzylate from rat brain muscarinic receptors and in vivo by insignificant antagonism of the cholinergic stimulation produced by physostigmine or oxotremorine. These data suggest that 10a may be clinically useful as a novel nontricyclic antidepressant which is devoid of anticholinergic side-effect liability. Further evaluation of 10a in nonrodent species is in progress.

Aggression↗
PubMed1982

(+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 2. Nuclear-substituted analogues of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and (+/-)-4,5-dihydro-2-ethyl-3-methyl-4-phenyl-3H-1,3-benzodiazepine as potential antidepressant agents.

Antidepressant-like activity, as evidenced by marked inhibition of tetrabenazine-induced ptosis, was previously reported for (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepine derivatives. Since optimal antitetrabenazine activity was associated with (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (9k, HRP 543) and the 2-ethyl-3-methyl analogue (10k), the synthesis and evaluation of nuclear-substituted derivatives of these two compounds was also investigated. The initial synthesis involved Friedel-Crafts acylation of substituted benzenes with 2-nitrophenylacetyl chloride to afford 1-aryl-2-(2-nitrophenyl)ethanones 2, which were converted in five steps to (+/-)-alpha-aryl-N-methyl-2-nitrobenzeneethanamines 7. Greater flexibility with respect to the introduction of nuclear substituents was achieved by conversion of 2-nitrotoluene derivatives to 2 via acylation of intermediate beta-(dimethylamino)-2-nitrostyrenes with various aroyl chlorides and hydrolysis. Reductive amination of 2 with methylamine and sodium cyanoborohydride afforded 7 directly and significantly reduced the number of synthetic steps. Reduction of 7a-j to diamines 8a-j and cyclization with appropriate ortho esters gave nuclear-substituted analogues of 9k and 10k. Marked antitetrabenazine activity was associated with many of these compounds. Significant enhancement of activity with respect to the unsubstituted analogues 9k and 10k was not observed, with the exception of 9c which appeared to be slightly more potent than 9k.

Amphetamine↗
PubMed1981

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 6. Synthesis, 13C NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives.

4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a mixture of cis- and trans-4-(dimethylamino)spiro[cyclohexane-1,1'(3'H)-isobenzofuran]-3'-ones (1a,b), which were separated by fractional crystallization. Addition of aryllithium or aryl Grignard reagents to 1a,b and formic acid reduction afforded cis- and trans-4-(dimethylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofurans] 3a-f, which were converted to secondary amine analogues 5a-e. Tentative stereochemical assignments are based on chemical arguments and are supported by 13C NMR chemical shift data. Marked inhibition of tetrabenazine-induced ptosis is a property of most antidepressants, and significant antitetrabenazine activity is observed for several of these compounds. Optimal antitetrabenazine activity is associated with the cis-3'-phenyl series, and the cis secondary amine 5a is approximately twice as potent as the cis tertiary amine 3a. The various compounds are relatively weak with respect to potentiation of L-5-hydroxytryptophan-induced seizures.

Animals↗
PubMed1979

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 5. Conformationally mobile analogues derived by furan ring opening.

Synthesis and antitetrabenazine activity of 4-[2-(arylmethyl)phenyl]piperidines and 4-(benzyloxy)-4-phenylpiperidines, prepared as simplified and possibly more readily synthesized analogues of 3-phenylspiro[isobenzofuran-1 (3H),4'-piperidine], are reported. Several 4-[2-(arylmethyl)phenyl]piperidines display antitetrabenazine activity comparable to imipramine or amitriptyline but are two- to fourfold less active than analogous 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Structure--activity relationships for 4-[2p(arylmethyl)phenyl]piperidines are generally similar to the profile established for 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Significant antitetrabenazine activity is associated only with derivatives where the arylmethyl group is ortho to the piperidine ring. 4-(Benzyloxy)-4-phenylpiperidines and 4-[2-(arylmethyl)phenyl]-4-piperidinols and the corresponding methyl ethers and esters display weak to modest antitetrabenazine activity. 4-[2-(Arylmethyl)phenyl]-1,2,3,6-tetrahydropyridine derivatives, at best, exhibit modest antitetrabenazine activity, with the exception of 4-[2-(phenylmethyl)phenyl]-1,2,3,6-tetrahydropyridine which is approximately equipotent with amitriptyline. The results of these investigations allow certain speculations to be made with respect to the role of the furan ring in the 3-arylspiro[isobenzofuran-1(3H),4'-piperidines] and antitetrabenazine activity.

Animals↗
PubMedDate not supplied

Expression and functional role of co-stimulatory molecules in CD40+IL-4-stimulated B cells from atopic and non-atopic donors.

As immunological dysregulation is a possible key defect in atopic diseases, we have studied the expression and function of costimulatory molecules in atopic dermatitis (AD) patients compared with normal controls. Using flow cytometry, we showed that CD80 and CD86 are expressed at increased levels on human peripheral B cells in both groups after stimulation with anti-CD40 and interleukin 4 (IL-4), but to a significantly higher extent in the AD group. Furthermore, baseline expression of CD80 and CD86 on peripheral B cells was low in normal donors and increased in AD donors. To study the functional role of the costimulatory molecules in CD40+IL-4-stimulated peripheral mononuclear cells from normal and atopic donors, proliferation and IgE production were analysed in the presence of antibodies against the receptors of the costimulatory molecules. In the presence of either anti-CD28 or anti-CTLA-4, cell proliferation and IgE synthesis were significantly enhanced in the atopic group in anti-CD40+IL-4-stimulated peripheral mononuclear cells. These findings suggest that interaction of CD80 and CD86 with their receptors CD28 and CTLA-4 selectively promotes cell activation, including proliferation and IgE production in CD40+IL-4-stimulated peripheral blood mononuclear cells from atopic donors. It remains to be elucidated whether these changes are primary, based on the genetic background of atopics, or whether they are induced secondarily in the context of atopic pathology.

Abatacept↗
PubMedDate not supplied

Sugar is not an aggravating factor in atopic dermatitis.

Patients with atopic dermatitis frequently blame food for worsening their eczema. Recently, a sugar-free diet has become very popular among German patients. In order to investigate whether sucrose is an aggravating factor in atopic dermatitis, we conducted a prospective study in 30 patients. Double-blind, placebo-controlled food challenges with sugar were performed during a sugar-free diet period, which was started one week prior to the first challenge. Study parameters included the SCORAD index and eosinophilic cationic protein levels, which were determined before diet, on food challenges and one day after. In 29 evaluable patients we observed no significant difference in study parameters after the verum challenge compared to the placebo challenge. From these results, we conclude that sugar is not an aggravating factor in atopic dermatitis, which contradicts the view of many patients and underlines the importance of evidence-based medicine in the guidance of patients.

Adolescent↗
PubMedDate not supplied

Effects of retinoids on in vitro and in vivo IgE production.

BACKGROUND: Retinoids modulate the growth and number of different cell types, including B cells. We could previously show that retinoic acid (RA) strongly inhibits CD40 + IL-4-mediated IgE production in vitro. The aim of the present study was to extend these findings regarding the potential use of retinoids for the treatment of allergic diseases. METHODS: In vitro IgE production was studied in anti-CD40 + IL-4-stimulated peripheral blood mononuclear cells (PBMC) from allergic donors in the presence of 10(-15)-10(-5) M all-trans and 13-cis RA and in ovalbumin (OVA)-sensitized BALB/c mice treated with RA (20 mg/kg) before and during sensitization. IgE and IgG1 levels were determined in the sera of the mice at day 21 after 2 injections (days 1 and 8) of aluminum hydroxide-absorbed OVA. RESULTS: All-trans and 13-cis RA inhibited in vitro IgE production from PBMC in a dose-dependent manner, but were more efficient in atopic dermatitis patients with low total serum IgE levels (< 400 kU/ml), maximal inhibition for all-trans RA at 10(-7) M (87%) and for 13-cis RA at 10(-5) M (96%) compared to patients with high serum IgE levels (>2,000 kU/ml), maximal inhibition for both all-trans and 13-cis RA at 10(-5) M (53 and 39%, respectively). In contrast, the in vivo data from OVA-sensitized mice revealed comparable total IgE and IgG1 levels in control versus all-trans RA or CD336-treated groups, specific IgE was even higher in the CD336-treated group (n = 10, 2,814 ng/ml), and was comparable in mice treated with OVA alone or with additional all-trans RA (n = 10, 1,447 and 1,354 ng/ml, respectively). CONCLUSIONS: These results indicate that the efficacy of retinoids to inhibit IgE production in vitro depends on the frequency of switched cells in the peripheral blood and that in an in vivo model using OVA-sensitized mice, retinoids fail to inhibit IgE production.

Allergens↗