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1.
Gesundheitswesen ; 75(3): 151-4, 2013 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22930195

RESUMO

In medical and public debates, the concept "personalized" or "individualized" medicine (PM) is increasingly used for the orientation of medicine towards individual genetic, molecular and biological characteristics. However, this tunnel view neglects that the human "person" or "individual" encompasses more than just the molecular and biological side, and that patients increasingly call for a more holistic and more person-centred form of health care. Therefore the authors propose to extend the concept of PM in the framework of an integrative health-care concept, so that with respect to a modern and patient-centred health-care system not only the biological, but also the relevant psychological, mental, social, cultural, spiritual, and economic aspects of the human individual are accounted for in health care. The Faculty of Health of Witten/Herdecke University proposes the term "integrative and personalised health care" for such a holistic form of PM.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Saúde Holística , Medicina de Precisão/métodos , Alemanha , Modelos Organizacionais
2.
J Physiol Pharmacol ; 61(1): 89-97, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20228420

RESUMO

This study was performed to assess whether mice lacking the cannabinoid receptor CB1, CB2 or both receptors show increased susceptibility to TNBS colitis in comparison to wildtype mice. Previously, activation of CB1 and CB2 receptors showed attenuation of TNBS colitis in mice. The aim of the study was to investigate the susceptibility of three mouse strains CB1-, CB2- and CB1+2 double knockout mice in the model of TNBS colitis. The different knockout mice were given each a single enema with TNBS 7 mg, volume 150 microl (in 50% ethanol solution) on day 1. Control group (C57BL/6 mice) received the same concentration of TNBS enema and each strain received vehicle application of 150 microl 50% ethanol solution. After a 3-day period, the animals were sacrificed and their colon excised. A scoring system was used to describe macroscopical and histological changes. Messenger RNA-expression of TNF-alpha and IL-1beta as pro-inflammatory markers was measured by RT-PCR. All three knockout strains showed increased susceptibility to TNBS colitis quantified by macroscopical and histological scoring systems and pro-inflammatory cytokine expression in comparison to the TNBS control group (wild type C57BL/6 animals). Mice lacking the CB1-, CB2-receptor or both receptors showed aggravation of inflammation in the model of TNBS colitis. Lacking of both cannabinoid receptors did not result in potentiation of colitis severity compared to lacking of each CB1 or CB2, respectively. These results suggest that the endocannabinoid system may have tonic inhibitory effects on inflammatory responses in the colon.


Assuntos
Colite/induzido quimicamente , Colite/metabolismo , Receptor CB1 de Canabinoide/deficiência , Receptor CB2 de Canabinoide/deficiência , Ácido Trinitrobenzenossulfônico/toxicidade , Animais , Colite/genética , Modelos Animais de Doenças , Predisposição Genética para Doença , Mediadores da Inflamação/toxicidade , Camundongos , Camundongos Endogâmicos AKR , Camundongos Endogâmicos C57BL , Camundongos Knockout , Projetos Piloto , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Índice de Gravidade de Doença
3.
Endoscopy ; 40(2): 106-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18197583

RESUMO

BACKGROUND AND STUDY AIMS: We aimed to determine the feasibility of obtaining selective fluorescence of precancerous/cancerous lesions in the colon with a new fluorescence video endoscope system in combination with the selective photosensitizer precursor hexaminolevulinate (HAL), and to carry out a dose-finding study with evaluation of the optimal dose and application time. PATIENTS AND METHODS: 12 patients with colorectal lesions underwent sensitization with locally applied HAL enemas in two concentrations (0.8 mmol and 1.6 mmol). The examination was conducted either 30 or 60 minutes after rectal administration of the sensitizer, using a special light source capable of delivering either white or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. Corresponding endoscopic, fluorescence, and microscopic findings were compared. RESULTS: Using histological findings as the gold standard, 52/53 of the premalignant/malignant lesions showed red fluorescence under the photodynamic diagnosis (PDD) examination; 38/53 were detected with white-light endoscopy. The PDD mode showed 28 % more polyps than did white-light endoscopic imaging. The greatest fluorescence intensity in precancerous lesions was found with retention for 60 minutes of 500 ml of 1.6 mmol HAL. CONCLUSIONS: Administration of HAL enema induces selective lesion fluorescence and increases the lesion detection rate in patients with colorectal adenoma and early carcinoma.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Neoplasias do Colo/patologia , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Fármacos Fotossensibilizantes , Lesões Pré-Cancerosas/diagnóstico , Idoso , Biópsia por Agulha , Neoplasias do Colo/prevenção & controle , Pólipos do Colo/patologia , Diagnóstico Precoce , Estudos de Viabilidade , Feminino , Fluorescência , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Sensibilidade e Especificidade
4.
Int J Colorectal Dis ; 22(7): 833-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16944185

RESUMO

Corticosteroids and 5-aminosalicylic acid are the primary standard therapy for inflammatory bowel disease. Recent immunologic data implicate an involvement of mast cell activation followed by increased histamine secretion and elevated tissue concentrations of histamine in the pathogenesis of ulcerative colitis. In the present case, the clinical course of a 35-year-old man with steroid-dependent chronic active ulcerative colitis, who did not respond to high-dose steroids, antibiotics, or azathioprine during 3 years, is reported. Clinical disease activity and established serological markers were recorded during 6 weeks of unsuccessful therapy and during the next 6 weeks, as a new nonsedative antihistaminergic drug, a mast cell stabilizer, and an hypoallergenic diet were implemented in addition to conventional therapy. Induction of remission was achieved within 2 weeks after treatment with fexofenadine, disodium cromoglycate, and an amino acid-based formula. Clinical disease activity, stool frequency, leukocytes, c-reactive protein, and orosomucoid levels in serum decreased rapidly. Daily steroid administration could be gradually reduced along with 6 weeks of this treatment. This report suggests that histamine and mast cell activity may be important pathophysiological factors responsible for persistent clinical and mucosal inflammatory activity in ulcerative colitis despite the use of steroids. In ulcerative colitis, patients unresponsive to conventional treatment, therapeutic considerations should also include an antiallergic approach when further signs of atopy or intestinal hypersensitivity are present.


Assuntos
Aminoácidos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Cromolina Sódica/uso terapêutico , Glucocorticoides/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Terfenadina/análogos & derivados , Administração Oral , Adulto , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Biópsia , Colite Ulcerativa/patologia , Colonoscopia , Quimioterapia Combinada , Seguimentos , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Humanos , Masculino , Indução de Remissão , Terfenadina/uso terapêutico
5.
Dtsch Med Wochenschr ; 131(7): 319-22, 2006 Feb 17.
Artigo em Alemão | MEDLINE | ID: mdl-16468101

RESUMO

HISTORY AND ADMISSION FINDINGS: Two men were hospitalized (three years apart) after aspirating petroleum on their fist attempt at "fire-eating". Pt.1 (aged 25 years) complained of chest pain, dyspnea and dizziness. The other (Pt. 2; aged 29 years) had a hemoptysis. Pt. 1 had a normal body temperature, but the breath sounds were decreased over the left base. The breath sounds in Pt. 2 were normal, but he had a fever of 38.8 degrees C. Routine physical examination was unremarkable. INVESTIGATIONS: Laboratory tests in both patients revealed increased inflammatory parameters. Chest radiographs showed that Pt. 1 had a left basal alveolar infiltrate, while Pt. 2 had an infiltrate in the right middle and upper lobe, which on computed tomography after a few days showed signs of cavitation in the left infrahilar region and the middle lobe, respectively. Pneumococci were found in the sputum of Pt. 2. TREATMENT AND COURSE: Both patients were given antibiotics, Pt. 1 also had salbutamol inhalation treatment. The patients were discharged symptom-free after 8 and 10 days, respectively. A follow-up chest radiograph four weeks later in Pt. 1 merely showed streaky-fibrotic residues. CONCLUSION: These two case reports and detailed literature search indicate that immediate administration of antibiotics is important, while routine steroid treatment is not necessary.


Assuntos
Antibacterianos/uso terapêutico , Petróleo/efeitos adversos , Pneumonia Aspirativa/etiologia , Administração por Inalação , Adulto , Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Dor no Peito , Tontura , Dispneia , Hemoptise , Humanos , Masculino , Pneumonia Aspirativa/diagnóstico , Pneumonia Aspirativa/tratamento farmacológico
6.
MMW Fortschr Med ; 147(41): 30-3, 2005 Oct 13.
Artigo em Alemão | MEDLINE | ID: mdl-16270508

RESUMO

Protection against infection encompasses appropriate medical treatment of existing diseases as well as counseling on social, psychological, disease-specific and individual factors--and this also applies to the old patient. In appropriate cases, complementary and alternative medicine (CAM) or relevant substances may be administered in addition to conventional medicine as supportive measures in preventing infection and preserving health. Acupuncture and homeopathy are widely established, and must be considered largely free of side effects. However, in light of the currently unsatisfactory situation in terms of good scientific studies, these forms of treatment cannot yet be definitively recommended. The administration of synthetic vitamins as dietary supplements may compensate deficiencies due to malnutrition or malabsorption problems in the elderly. However, neither supplementation with vitamin C or E, nor zink has any positive effect as cold treatment. The latest studies also fail to show any prophylactic effect of Echinacea extracts on the duration or severity of colds.


Assuntos
Infecções Comunitárias Adquiridas/prevenção & controle , Terapias Complementares , Banho a Vapor , Idoso , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sudorese , Resultado do Tratamento
8.
Appl Microbiol Biotechnol ; 67(2): 197-201, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15578180

RESUMO

The effects of methyl jasmonate (MJ) elicitation on the cell growth and accumulation of ginsenoside in 5-l bioreactor suspension cultures of Panax ginseng were investigated. Ginsenoside accumulation was enhanced by elicitation by MJ (in the range 50-400 microM); however, fresh weight, dry weight and growth ratio of the cells was strongly inhibited by increasing MJ concentration. The highest ginsenoside yield was obtained at 200 microM MJ. In the second experiment, 200 microM MJ was added on day 15 during the cultivation. The ginsenoside, Rb group, and Rg group ginsenoside content increased 2.9, 3.7, and 1.6 times, respectively, after 8 days of MJ treatment. Rb group gisnsenosides accumulated more than Rg group ginsenosides. Among Rb group ginsenosides, Rb1 content increased significantly by four times but the contents of Rb2, Rc and Rd increased only slightly. Among Rg group ginsenosides, Rg1 and Re showed 2.3-fold and 3.0-fold increments, respectively, whereas there was only a slight increment in Rf group ginsenosides. These results suggest that MJ elicitation is beneficial for ginsenoside production using 5-l bioreactor cell suspension cultures.


Assuntos
Acetatos/farmacologia , Reatores Biológicos , Ciclopentanos/farmacologia , Ginsenosídeos/biossíntese , Panax/metabolismo , Oxilipinas , Suspensões
9.
Allergy ; 59(9): 953-60, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15291903

RESUMO

BACKGROUND: Patients with allergic rhinitis (AR) increasingly use complementary medicine. The aim of this study was to determine whether traditional Chinese therapy is efficacious in patients suffering from seasonal AR. METHODS: Fifty-two patients between the ages of 20 and 58 who had typical symptoms of seasonal AR were assigned randomly and in a blinded fashion to (i) an active treatment group which received a semi-standardized treatment of acupuncture and Chinese herbal medicine, and (ii) a control group which received acupuncture applied to non-acupuncture points in addition to a non-specific Chinese herbal formula. All patients received acupuncture treatment once per week and the respective Chinese herbal formula as a decoction three times daily for a total of 6 weeks. Assessments were performed before, during, and 1 week after treatment. The change in severity of hay fever symptoms was the primary outcome measured on a visual analogue scale (VAS). RESULTS: Compared with patients in the control group, patients in the active treatment group showed a significant after-treatment improvement on the VAS (P = 0.006) and Rhinitis Quality of Life Questionnaire (P = 0.015). Improvement on the Global Assessment of Change Scale was noted in 85% of active treatment group participants vs 40% in the control group (P = 0.048). No differences between the two groups could be detected with the Allergic Rhinitis Symptom Questionnaire. Both treatments were well-tolerated. CONCLUSIONS: The results of this study suggest that traditional Chinese therapy may be an efficacious and safe treatment option for patients with seasonal AR.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Rinite Alérgica Sazonal/terapia , Terapia por Acupuntura/efeitos adversos , Adulto , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica Sazonal/psicologia , Método Simples-Cego
10.
Regul Pept ; 120(1-3): 39-51, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15177919

RESUMO

Ghrelin, identified in the gastric mucosa has been involved in control of food intake and growth hormone (GH) release but little is known about its influence on gastric secretion and mucosal integrity. The effects of ghrelin on gastric secretion, plasma gastrin and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) were determined. Exogenous ghrelin (5, 10, 20, 40 and 80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS and this was accompanied by the significant rise in plasma ghrelin level, gastric mucosal blood flow (GBF) and luminal NO concentrations. Ghrelin-induced protection was abolished by vagotomy and attenuated by suppression of COX, deactivation of afferent nerves with neurotoxic dose of capsaicin or CGRP(8-37) and by inhibition of NOS with L-NNA but not influenced by medullectomy and administration of 6-hydroxydopamine. We conclude that ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol and WRS, and these effects depend upon vagal activity, sensory nerves and hyperemia mediated by NOS-NO and COX-PG systems.


Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Mucosa Gástrica/irrigação sanguínea , Hormônios Peptídicos/uso terapêutico , Gastropatias/prevenção & controle , Adrenérgicos/administração & dosagem , Animais , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Capsaicina/farmacologia , Ciclo-Oxigenase 1 , Ácido Gástrico/metabolismo , Mucosa Gástrica/patologia , Gastrinas/sangue , Grelina , Hormônio do Crescimento/metabolismo , Isoenzimas/metabolismo , Masculino , Proteínas de Membrana , Mióticos/farmacologia , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Oxidopamina/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Wistar , Gastropatias/etiologia , Gastropatias/patologia , Vagotomia , Nervo Vago/efeitos dos fármacos , Nervo Vago/metabolismo
11.
Anticancer Res ; 24(1): 385-91, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15015625

RESUMO

BACKGROUND AND AIMS: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-Fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) and folinic acid (FA) (AIO-regimen) plus Oxaliplatin (L-OHP) after pre-treatment with the AIO regimen, focusing in particular on the efficacy of palliative first- and second-line treatment in colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous palliative first-line treatment in accordance with the AIO regimen. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m2 L-OHP in the form of a 2-hour intravenous (i.v.) infusion and 500 mg/m2 FA as a 1 to 2-hour i.v. infusion, followed by 2,600 mg/m2 5-FU administered as a 24-h inf. i.v. once weekly. A single treatment cycle comprised 6 weekly infusions followed by 2 weeks of rest. RESULTS: During second-line treatment, a total of 26 patients received 340 chemotherapy applications. As the main symptom of toxicity, diarrhoea (NCI-CTC toxicity grade 3+4) presented in 5 patients (19%; 95% CI: 4-34), followed by nausea (CTC grade 3) in one patient (4%; 95% CI: 0-11). Twenty-three patients were evaluable for treatment response. The remission data can be summarised as follows: Complete remission (CR): n=1 (4%; 95% CI: 0-13); partial remission (PR): n=3 (13%; 95% CI: 0-27); stable disease (SD): n=11 (48%; 95% CI: 27-68) and progressive disease (PD): n=8 (35%; 95% CI: 15-54). The median progression-free survival (PFS) rate (n=26) was 3.3 months (range 0-11.5), the median survival time counted from the start of second-line treatment (n=26) 11.6 months (range 2.1-33.0) and the median survival time counted from the start of first-line treatment (n=26) 19.9 months (range 7.7-49.8). CONCLUSION: Palliative second-line treatment according to the AIO regimen plus L-OHP is feasible in an outpatient setting and well tolerated by the patients. Tumour control (CR + PR + SD) was achieved in 65% of the patients, the median survival time being 11.6 months. The AIO regimen followed by the 'AIO regimen plus L-OHP' therapy sequence led to a promising median survival time of 19.9 months (range 7.7-49.8).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Cuidados Paliativos/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina
12.
Inflamm Res ; 52(9): 359-65, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14504662

RESUMO

OBJECTIVE AND DESIGN: The aim of the present study was to investigate, whether sensory nerves are involved in the gastroprotection induced by NO releasing non-steroidal anti-inflammatory drugs (NO-NSAID). MATERIAL: Studies were performed in Wistar rats with intact or inactivated sensory nerves by pretreatment with large dose of capsaicin (125 mg/kg sc). TREATMENTS: Acute gastric lesions were induced by 100% ethanol (100% EtOH). 1 h before exposure to 100% EtOH, rats received vehicle, aspirin (ASA) or NO-releasing aspirin (NO-ASA) in the same dose (50 mg/kg). The animals were killed 1 h after exposure to 100% EtOH. METHODS: Determinations were made of gastric mucosal injury, mucosal gastric blood flow, mucosal mRNA expression of glutathione peroxidase (GPx), zinc copper superoxide dismutase (SOD) and heat shock protein (HSP70) by RT-PCR and protein expression for HSP70 by Western blotting. RESULTS: Pretreatment with ASA aggravated the acute gastric injury induced by 100% EtOH, whereas pretreatment with NO-ASA led to a significant reduction in this injury. Administration of 100% EtOH was accompanied by a pronounced upregulation of HSP70, which was reduced by ASA, but enhanced by NO-ASA application. Sensory deactivation with capsaicin enhanced acute ethanol lesions and led to a significant attenuation in HSP70 expression. In contrast to ASA, NO-ASA attenuated gastric mucosal lesions and significantly upregulated HSP70 expression despite blockade of sensory nerves. NO-ASA, but not ASA, caused an upregulation of SOD and GPx mRNA in gastric mucosa with or without sensory denervation. CONCLUSIONS: NO-ASA protects gastric mucosa even after blockade of sensory nerves due to the upregulation of HSP70 expression and attenuation of the oxidative injury resulting from strong upregulation of genes for antioxidant enzymes.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/inervação , Óxido Nítrico/farmacologia , Células Receptoras Sensoriais/fisiologia , Animais , Aspirina/análogos & derivados , Western Blotting , Capsaicina/farmacologia , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/patologia , Glutationa Peroxidase/genética , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle , Superóxido Dismutase/genética
13.
Int J Oncol ; 23(3): 751-6, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12888913

RESUMO

The prognosis of advanced colorectal carcinoma (CC) is poor. Established chemotherapy shows only limited efficacy but significant side effects. We investigated how far a combination of tamoxifen (TAM), 9-cis-retinoic acid (CRA) and the fluoroquinolone ciprofloxacin (CIP) synergize to inhibit proliferation and promote apoptosis of CC cells in vitro. The CC cell lines LOVO, CC-531 and SW-403 were incubated with TAM, CRA and CIP (10(minus;4)-10(minus;6) M) as single agents and in combination. Cell proliferation was assessed by bromodeoxyuridin incorporation. Apoptosis was quantified immunohistochemically and by FACS analysis after staining with propidium iodide. Changes in the expression of caspase 3, bax, bcl-2 and p21cip/waf were assessed by quantitative Western blotting. CRA and TAM monotherapy was moderately effective. Their combination enhanced apoptosis from 60% to more than 80% in all cell types. Apoptosis was paralleled by inhibition of proliferation and further potentiated by addition of CIP. The combination effectively up-regulated caspase 3 and bax and down-regulated bcl-2 and p21cip/waf. Combinations of biomodulaters act synergistically to inhibit proliferation and promote apoptosis in CC cells. Due to their known safety profile, this justifies clinical trials for colorectal cancer using combinations of these biological response modifiers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Alitretinoína , Western Blotting , Bromodesoxiuridina/farmacologia , Caspase 3 , Caspases/biossíntese , Divisão Celular , Linhagem Celular Tumoral , Separação Celular , Ciprofloxacina/administração & dosagem , Neoplasias do Colo/patologia , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/biossíntese , DNA/metabolismo , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Indicadores e Reagentes/farmacologia , Cinética , Prognóstico , Propídio/farmacologia , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Tamoxifeno/administração & dosagem , Fatores de Tempo , Tretinoína/administração & dosagem , Proteína X Associada a bcl-2
14.
Anticancer Res ; 23(2C): 1773-7, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12820457

RESUMO

BACKGROUND AND AIMS: The aim of this work was to investigate the relationship between microsatellite instability (MSI), treatment response and survival in palliative patients with colorectal cancer (CRC) undergoing first-line treatment with weekly 24-hour infusion (24-h inf.) of high-dose 5-fluorouracil (5-FU) and folinic acid (FA). PATIENTS AND METHODS: Tumour material from the colorectal primary carcinomas was analysed for 43 patients. MSI analysis was carried out and immunohistochemistry was performed with hMLH1 and hMSH2. RESULTS: Tumours of 7 patients (16%) were highly instable (MSI-H). These patients had a better response rate (72% vs. 41%; p = 0.072) and a significantly better median survival (33 months, [95% CI 20-46] vs. 19 months, [95% CI 10-28]; p = 0.021) than microsatellite stable (MSS) patients (n = 36). Furthermore, MSI status was shown to be an independent predictive marker for survival (p = 0.037). CONCLUSION: These data provide further support for the hypothesis that MSI-H CRC might have a better response and survival than (MSS) CRC in palliative first-line treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA , Repetições de Microssatélites/genética , Cuidados Paliativos , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Proteínas de Transporte , Neoplasias Colorretais/metabolismo , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Imuno-Histoquímica , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/biossíntese , Proteínas Nucleares , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas/biossíntese , Taxa de Sobrevida , Resultado do Tratamento
15.
Scand J Gastroenterol ; 38(5): 565-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12795472

RESUMO

We report on two cases of acute liver injury along with the intake of Greater Celandine (Chelidonium majus), a well-known herbal remedy frequently used for irritable bowel syndrome. All other possible causes of acute liver damage were excluded in both patients. In one patient, cholestatic hepatitis recurred rapidly after involuntary re-exposition. Both patients fully recovered after the withdrawal of Greater Celandine. The two cases add to the existing database about the potential hepatotoxicity of drugs containing Greater Celandine and raise the question whether the approval of this drug should be re-evaluated in the light of lacking evidence for a therapeutic benefit.


Assuntos
Chelidonium/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicina Herbária/métodos , Adulto , Idoso , Colestase/induzido quimicamente , Feminino , Humanos , Masculino
16.
Z Gastroenterol ; 41(4): 333-42, 2003 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-12695940

RESUMO

Alcoholic liver disease is the most frequent organ damage encountered in chronic alcoholics and the annual death rate attributed to alcohol-induced end-stage liver disease exceeds that of car accidents. Alcoholic liver damage occurs mainly due to the toxicity of its first metabolite acetaldehyde, and due to interactions with numerous macro- and micronutrients. Established treatment options comprise psychotherapy aiming to achieve abstinence, nutritional therapy, management of hepatological complications, and liver transplantation in selected individuals. Since these therapeutic approaches are unsuccessful in many patients, pharmacological therapies of alcoholic liver disease are being investigated. Many drugs failed to be beneficial or have even shown toxicity. However, some agents are promising, such as S-adenosyl-L-methionine (SAMe), pentoxifylline, metadoxin, polyenylphosphatidylcholine or inhibitors of the cytochrome P450 2E1 isoenzyme. In severely ill patients with alcoholic hepatitis, drugs with anti-tumor necrosis factor alpha activity are currently investigated in clinical trials. If and how far corticosteroids are beneficial remains controversial and their use should be restricted to selected patients. Anabolic steroids used to enhance the nutritional status may lead to serious side effects while having a marginal benefit. Silymarin has not been proven efficacious in alcoholic cirrhosis and clinical trials are ongoing which aim to elucidate its therapeutic value in less advanced stages of liver disease.


Assuntos
Hepatopatias Alcoólicas/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Drogas em Investigação/uso terapêutico , Humanos , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/mortalidade , Testes de Função Hepática , Taxa de Sobrevida , Resultado do Tratamento
17.
Oncology ; 64(2): 131-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12566910

RESUMO

PURPOSE: To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC). PATIENTS AND METHODS: 20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up. RESULTS: After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3-4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12-38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%. CONCLUSION: The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Terapia Neoadjuvante , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Z Gastroenterol ; 40(10): 881-4, 2002 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-12436355

RESUMO

The most commonly used treatment in the palliative first-line therapy of metastatic pancreatic adenocarcinoma is the Gemcitabine (Gem) monotherapy, while several combination therapies are currently being tested in clinical trials. With regard to pancreatic cancer, a palliative second-line therapy has not been established, yet. The four patients presented in this paper received a palliative second-line therapy with Oxaliplatin (L-OHP), Gem and high-dose 5-Fluorouracil (5-FU) as a 24-h infusion after a first-line therapy with Gem and weekly high-dose 5-FU as a 24-h infusion. During second-line therapy, four patients received 67 chemotherapy applications, which were well tolerated. As severe symptom of toxicity, thrombocytopenia (CTC toxicity grade 4) was observed in one patient. As a result of second-line therapy, stable disease (SD) with a significant decrease of CA 19 - 9 was achieved in three patients and partial remission (PR) in one patient. After palliative first- and second-line treatment the survival time of the patients was 9, 9, 15 and 20 months. Currently, a multicentre phase I study has been started aiming at an optimisation of the three-drug combination dosage.


Assuntos
Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Hepáticas/secundário , Cuidados Paliativos , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Retratamento , Gencitabina
19.
Hepatogastroenterology ; 49(46): 1102-8, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12143213

RESUMO

Cirrhosis of the liver is a major complication of various chronic liver diseases and results from excess production and decreased degradation of extracellular matrix. Proinflammatory cytokines, toxic metabolites and certain drugs can trigger enhanced fibrogenesis in hepatic stellate cells and myofibroblasts, the major matrix-producing cells. Since treatment of established cirrhosis is limited, therapeutic interventions that inhibit or mitigate fibrogenesis are needed. Numerous drugs have been investigated for their antifibrotic potential and botanicals constitute a significant fraction of them. Colchicine has been used to treat various chronic liver diseases with controversial results. To date, there is a lack of studies in appropriate animal models and well-controlled human trials to demonstrate its antifibrotic properties. Silymarin has so far failed to clearly show an antifibrotic effect in human studies, whereas animal experiments suggest that this mixture of flavolignanes may be beneficial in patients which have not yet developed cirrhosis. Animal studies indicate an antifibrotic potential of Shosaiko-to, a herbal combination frequently used in China and Japan for the treatment of chronic viral hepatitis, but mechanisms of action need to be further explored. Other botanicals include trans-resveratrol, a flavonoid extracted from grapevine, and Salvia miltiorrhiza which were shown to interfere with the process of hepatic stellate cell activation. Herbal combinations, such as compound 861 and LIV.52 were advocated as antifibrotics or hepatoprotectives, but studies in humans have either been of questionable design or resulted in cessation of the trial due to adverse outcomes.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/tratamento farmacológico , Fitoterapia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Ensaios Clínicos como Assunto , Colágeno/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/patologia
20.
Psychother Psychosom ; 70(3): 151-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11340417

RESUMO

BACKGROUND: 'Functional relaxation' (FR) according to Marianne Fuchs is a body-oriented psychotherapy that involves teaching the patient a type of relaxation techniques aimed at maintaining equilibrium of the nervous system. METHODS: In order to determine whether the practice of elementary parts of this therapy has an immediate beneficial effect on pulmonary function, a randomized, single-blind, prospective crossover study was done with 21 asthmatics with acute bronchoconstriction. On 3 consecutive days they were given either (1) a 5-min verbal standard instruction in elementary exercises of FR (eFR), which they were to practice during subsequent bodyplethysmographic measurement or (2) inhalative terbutaline (IT), a beta(2)-sympathomimetic drug, or (3) an unspecific 'placebo relaxation' technique (PRT), so that all subjects tried all 3 treatments in random order. Spirometric variables were assessed. RESULTS: There was a significant decrease in specific airway resistance with eFR, which, though not as pronounced as with IT, was significantly greater than with PRT. This study shows that clinically relevant effects can be achieved for patients with asthma through mind-body interaction, which can be triggered by reproducible procedures. CONCLUSION: Further development of the FR approach could lead to a nonpharmacological and effective supplementary treatment for asthma, which is in high demand by many patients.


Assuntos
Asma/terapia , Terapia de Relaxamento , Simpatomiméticos/uso terapêutico , Terbutalina/uso terapêutico , Doença Aguda , Adulto , Idoso , Asma/tratamento farmacológico , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
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