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INTRODUCTION: MRI often induces anxiety, leading to incomplete scans and claustrophobia-related distress. Open MRI systems aim to enhance patient comfort. This study examines how prior MRI experiences impact subsequent encounters in an open upright MRI scanner. METHODS: In this cross-sectional study, 118 adult patients completed a self-administered questionnaire from August 2022 to October 2023. It covered previous MRI experiences, including questions about claustrophobia, premature scan terminations, sedative medication usage, general MRI experiences, and interactions with radiology technologists. RESULTS: Patients in open upright MRI reported less claustrophobia compared to closed MRI systems (18.4% vs. 58.3%), fewer premature scan terminations (5.3% vs. 31.0%), and less sedative use (5.3% vs. 46.9%). Moderate positive correlations were found between past and current claustrophobic events and premature scan terminations. Effective communication with radiology technologists was essential for patient comfort and reduced claustrophobia. Scan duration and noise triggered discomfort in 26.1% and 21.6% of study participants respectively. Persons without prior MRI experience were more satisfied with the examination and expressed no clear preference for future MRI settings, contrasting those with previous exposure favoring the open MRI setup. CONCLUSION: The study emphasizes the benefits of open upright MRI for high-risk claustrophobic patients. It identifies the lasting impact of negative MRI experience on future examinations and highlights the crucial role of radiology technologists. IMPLICATIONS FOR PRACTICE: Integrating open MRI scanners in medical facilities and prioritizing effective communication with radiology technologists enhances patient comfort. Positive experiences with open MRI may improve patient compliance and offer greater flexibility for future examinations.
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OBJECTIVE: Research in the USA has demonstrated numerous associations between adult attention-deficit/hyperactivity disorder (ADHD) and smoking behaviour; however, no specific work on this topic has been done in Switzerland. The aim of the study was to gain knowledge about the association between ADHD and tobacco consumption in a Swiss sample of adult ADHD patients. METHODS: The study subjects were recruited from patients with a DSM-IV diagnosis of ADHD consecutively presenting to the ADHD consultation service at the Centre for Addiction Disorders, an outpatient facility of the Zurich University Hospital, between September 2000 and January 2006. Complete data could be obtained from 100 of 134 patients presenting to the service. RESULTS: The number of current smokers in the ADHD sample was significantly elevated compared to the Swiss general population (55 vs 31%). Additionally, daily smokers in the ADHD sample smoked significantly more cigarettes per day, reported higher levels of nicotine dependence and started to smoke regularly at a significantly younger age. The motivation to quit smoking was high. CONCLUSIONS: The results of this Swiss study are consistent with previous research in the USA. The fact that many adults with ADHD are motivated to quit smoking and that they actually make use of support in quitting is crucial for secondary tobacco prevention.
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Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/epidemiologia , Adulto , Causalidade , Comorbidade , Feminino , Humanos , Incidência , Masculino , Medição de Risco , Fatores de Risco , Suíça/epidemiologiaRESUMO
Despite the large number of studies dealing with dementia caregivers in Europe, a valid German version of the most widely used measurement of caregiver burden, the Zarit Burden Interview, has not been published. The purpose of this study was to evaluate the psychometric properties of the German Zarit Burden Interview (G-ZBI). A sample of community-dwelling older couples (n=37) with the husband suffering from dementia and the wife being the primary caregiver participated in this study. The G-ZBI and related constructs were assessed in order to test for reliability and construct validity. The G-ZBI revealed psychometric properties comparable with those of the original instrument and empirically validated translations. Results indicate high internal consistency (Cronbach's alpha=0.91) and good validity due to strong correlations with caregiver life satisfaction and depression, as well as patients' dependency, neuropsychiatric symptoms, and dementia severity. The psychometric qualities of the G-ZBI indicate that it is both a reliable and valid instrument to assess caregiver burden and to detect highly stressed individuals.
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Doença de Alzheimer/enfermagem , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Comparação Transcultural , Assistência Domiciliar/psicologia , Inquéritos e Questionários , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Cônjuges/psicologia , Suíça , TraduçãoRESUMO
Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 microg/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4(+) memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123(+) plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-gamma production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa.
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Doença de Crohn/tratamento farmacológico , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Interleucina-10/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Doença de Crohn/imunologia , Citocinas/imunologia , Esquema de Medicação , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Ativação Linfocitária/imunologia , Masculino , Mucosa/imunologia , Projetos Piloto , Proteínas Recombinantes , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Primary carcinoma of the Bartholin's gland is rare, consequently standard management is not clear. Although the sentinel concept has gained popularity for other malignancies of the female reproductive tract, the literature lacks reports of this approach for carcinomas of the Bartholin's gland. CASE: We present a patient with stage I adenocarcinoma of the Bartholin's gland. She was managed with wide excision and inguinal and laparoscopic pelvic sentinel lymphadenectomy followed by complete pelvic lymphadenectomy. We discuss the rationale for the sentinel concept. CONCLUSION: As for other gynaecological malignancies the sentinel lymphadenectomy seems to be an appropriate and feasible surgical approach for early stage carcinomas of the Bartholin's gland.
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Adenocarcinoma/patologia , Glândulas Vestibulares Maiores/patologia , Linfonodos/patologia , Neoplasias Vulvares/patologia , Adenocarcinoma/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela , Neoplasias Vulvares/cirurgiaRESUMO
Mastodynia is correlated with the menstrual cycle. Using frequency-domain near-infrared spectroscopy (FD-NIRS), we investigated changes in breast perfusion in women who were or were not using hormonal contraception. Healthy volunteers, on or not on hormonal contraception, were examined. Optical properties were measured in all quadrants of both breasts, and physiological parameters were calculated. Measurements were repeated every other day during one complete menstrual cycle. Measurements were comparable in all quadrants. Data remained unchanged during the entire cycle in patients using hormonal contraception. However, a biphasic variation of deoxyhemoglobin, oxyhemoglobin, total hemoglobin (tHb), and water content (H(2)O) was observed in women not using contraception. tHb and H(2)O distinctly increased during the ovulation period and remained elevated throughout the luteal phase. It was concluded that FD-NIRS allows accurate measurement of optical properties of human breasts. As opposed to the menstrual cycles of persons using oral contraception, spontaneous menstrual cycles exhibit biphasic variations of tissue perfusion parameters. These findings are important for the investigation of mastodynia.
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Mama/irrigação sanguínea , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Mama/efeitos dos fármacos , Mama/fisiologia , Anticoncepcionais Orais/administração & dosagem , Feminino , Hemoglobinas/metabolismo , Humanos , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Fenômenos Ópticos , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Adulto JovemAssuntos
Cesárea , Embolia Amniótica , Ressuscitação , Humanos , Embolia Amniótica/terapia , Embolia Amniótica/diagnóstico , Feminino , Gravidez , AdultoRESUMO
Bone marrow transplantation (BMT) is currently used for the treatment of a variety of neoplastic diseases. However, significant obstacles limiting the efficacy of allogeneic BMT are the occurrence of graft-versus-host disease (GvHD) and tumor relapse. Natural killer (NK) cells exert a variety of immunologic and homoeostatic functions. We examined whether adoptive transfer of activated NK cells of donor type would prevent GvHD after allogeneic BMT in mice. Lethally irradiated C57BL/6 (H-2(b)) mice, were transplanted with MHC incompatible BALB/c (H-2(d)) bone marrow cells and spleen cells and rapidly succumbed to acute GvHD. In contrast, mice that also received activated NK cells of donor type exhibited significant increases in survival. In determining the mechanism by which the NK cells prevented GvHD, mice were concurrently treated with a neutralizing antibodies to the immunosuppressive cytokine TGFbeta. Anti-TGFbeta completely abrogated the protective effects of the activated donor NK cells indicating that TGFbeta plays an important role in the prevention of GvHD by NK cells. We then examined whether activated NK cells of donor type after allogeneic BMT would induce graft-versus-tumor (GvT) effects without GvHD in mice bearing a murine colon adenocarcinoma (MCA-38). 10 d after receiving the tumor, in which the mice had demonstrable lung metastases, recipients received an allogeneic BMT with or without activated NK cells. Administration of activated NK cells resulted in significant GvT effects after allogeneic BMT as evidenced by increases in median survival and fewer lung metastasis. No evidence of GVHD was detected compared with recipients receiving spleen cells alone which also developed fewer lung metastases but in which all had succumbed to GVHD. Thus, our findings suggest that adoptive immunotherapy using activated donor NK cells combined with allogeneic BMT inhibits GvHD and promotes GvT in advanced tumor-bearing mice. These results also suggest that GvT and GvHD can be dissociable phenomena.
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Adenocarcinoma/terapia , Transplante de Medula Óssea/imunologia , Neoplasias do Colo/terapia , Doença Enxerto-Hospedeiro/prevenção & controle , Células Matadoras Naturais/transplante , Adenocarcinoma/imunologia , Transferência Adotiva , Animais , Neoplasias do Colo/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Imunossupressores/farmacologia , Interleucina-2/farmacologia , Intestinos/imunologia , Intestinos/patologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Fígado/imunologia , Fígado/patologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos SCID , Pele/imunologia , Pele/patologia , Fatores de Tempo , Fator de Crescimento Transformador beta/imunologia , Transplante HomólogoRESUMO
The beta2-adrenergic receptor (beta2AR), an important modulator of cardiac inotropy and chronotropy, has significant genetic heterogeneity in the population. Because dysfunctional betaARs play a role in the pathogenesis of the failing ventricle, we tested the hypothesis that beta2AR polymorphisms alter the outcome of congestive heart failure. 259 patients with NYHA functional class II-IV heart failure due to ischemic or dilated cardiomyopathy were genotyped and prospectively followed, with the endpoint defined as death or cardiac transplantation. The allele frequencies between this group and those of 212 healthy controls also were compared and did not differ between the groups. However, those with the Ile164 polymorphism displayed a striking difference in survival with a relative risk of death or cardiac transplant of 4.81 (P < 0.001) compared with those with the wild-type Thr at this position. Age, race, gender, functional class, etiology, ejection fraction, and medication use did not differ between these individuals and those with the wild-type beta2AR, and thus the beta2AR genotype at position 164 was the only clear distinguishing feature between the two groups. The 1-yr survival for Ile164 patients was 42% compared with 76% for patients harboring wild-type beta2AR. In contrast, polymorphisms at amino acid positions 16 (Arg or Gly) or 27 (Gln or Glu), which also alter receptor phenotype, did not appear to have an influence on the course of heart failure. Taken together with cell-based and transgenic mouse results, this study establishes a paradigm whereby genetic variants of key signaling elements can have pathophysiologic consequences within the context of a disease. Furthermore, patients with the Ile164 polymorphism and heart failure may be candidates for earlier aggressive intervention or cardiac transplantation.
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Insuficiência Cardíaca/genética , Isoleucina/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Adulto , Alelos , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/terapia , Feminino , Frequência do Gene , Genótipo , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Isquemia Miocárdica/genética , Isquemia Miocárdica/terapia , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
The investigational drug flavone acetic acid (FAA) systemically augments natural killer (NK) cell activity in normal and tumor-bearing mice and in human cancer patients. The results from the present investigation demonstrate that in vivo administration of FAA induces in a dose-dependent manner high levels of serum interferon (IFN) within 4 hours in BALB/c, C57BL/6, and BALB/c nude mice. Antibody neutralization studies indicated that FAA induced IFN of the alpha/beta type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN alpha mRNA in splenic leukocytes. In vivo administration of anti-IFN alpha/beta antibodies to FAA-treated mice inhibited the FAA-induced augmentation of splenic NK cell activity at 4 hours. These results suggest that FAA mediates its anti-tumor effects indirectly by immunomodulation as well as directly by antiproliferative or cytotoxic activity.
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Adjuvantes Imunológicos/farmacologia , Flavonoides/farmacologia , Interferon Tipo I/biossíntese , Células Matadoras Naturais/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Interferon Tipo I/análise , Interferon Tipo I/imunologia , Células Matadoras Naturais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , RNA Mensageiro/biossíntese , Fatores de TempoRESUMO
BACKGROUND: Persistence of the underlying malignancy remains the main obstacle to the successful treatment of human malignancies with high-dose chemoradiotherapy and bone marrow transplantation. PURPOSE: The aim of this study was to determine whether antigen-specific antitumor immune responses, elicited in normal donor mice by immunization with the soluble form of a surrogate tumor antigen (i.e., ovalbumin [OVA]), can be transferred via bone marrow transplantation into lethally irradiated, syngeneic recipient mice. An additional goal was to evaluate the ability of these adoptively transferred bone marrow cells to eradicate established recombinant OVA-expressing lymphomas that recurred after lethal-dose total-body irradiation (TBI). METHODS: Female C57BL/6 donor mice were immunized twice with OVA emulsified in a muramyl-dipeptide-containing adjuvant. Syngeneic mice bearing a day-10 or day-11, approximately 1-cm subcutaneous E.G7-OVA tumor (E.G7-OVA tumor cells were derived from transfection of EL-4 thymoma tumor cells using the coding sequence of chicken OVA gene complementary DNA) were treated with TBI and reconstituted with bone marrow from nonimmune or OVA-immunized mice. In subsequent experiments, tumor-bearing mice, treated with TBI and OVA-immune bone marrow, were given additional therapy either with a single OVA immunization or by the adoptive transfer of 1 x 10(7) in vitro activated spleen cells derived from OVA-immune donor mice and cultured 5 days with irradiated E.G7-OVA cells before transfer. RESULTS: E.G7-OVA tumor-bearing mice given TBI and OVA-immune bone marrow showed a significantly increased cure rate when compared with that among controls reconstituted with nonimmune bone marrow after TBI (logrank, P < .01). The antitumor effect of immune bone marrow was abrogated by T-cell depletion of the marrow graft (P < .016). The antitumor effect of immune marrow was enhanced by the addition of OVA immunization of tumor-bearing recipients (P < .015). OVA-specific cytotoxic T-lymphocyte (CTL) activity was recovered from tumor-bearing recipients of immune marrow 14 days after bone marrow transplantation. The antitumor effect observed following the adoptive transfer of immune marrow was further augmented by the addition of 1 x 10(7) splenic E.G7-OVA-specific in vitro activated CTLs derived from OVA-immune mice (P < .03). CONCLUSION: These studies establish the principle that antigen-specific T-cell immunity against a defined tumor-specific antigen can be transferred with bone marrow from an immune donor. IMPLICATIONS: Active immunization of normal human bone marrow or T-cell donors with a refined, safe tumor antigen and transfer of immunity to the patient may represent a novel strategy for circumventing the obstacle of host immune suppression associated with the tumor-bearing state.
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Transplante de Medula Óssea/imunologia , Imunoterapia Adotiva/métodos , Linfoma/terapia , Neoplasias Induzidas por Radiação/terapia , Linfócitos T/imunologia , Animais , Antígenos de Neoplasias , Epitopos , Feminino , Regulação Neoplásica da Expressão Gênica , Linfoma/imunologia , Linfoma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Induzidas por Radiação/imunologia , Neoplasias Induzidas por Radiação/metabolismo , Ovalbumina/biossíntese , Análise de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners.
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Poluição do Ar em Ambientes Fechados/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Radônio/efeitos adversos , Adulto , Idoso , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mineração , Risco , Distribuição por Sexo , Fumar/efeitos adversos , Fatores de TempoRESUMO
We have examined the ability of bryostatin 1 to inhibit the in vitro growth and in vivo development of a panel of four murine tumors of diverse tissue origins. A wide range of antiproliferative responses was observed for the four tumors. At 100 ng/ml the in vitro growth of the Renca renal adenocarcinoma, the B16 melanoma, the M5076 reticulum cell sarcoma, and the L10A B-cell lymphoma were inhibited by 0, 40, 40, and 94% respectively. All three cell lines sensitive to bryostatin in vitro responded to multiple dose, 1 microgram/injection/day in vivo i.p., bryostatin therapy. Only the in vitro resistant Renca tumor failed to respond to bryostatin in vivo. The correlation between in vitro and in vivo antitumor efficacy suggests a direct mechanism of antitumor activity for bryostatin. Both local regional therapy (M5076 i.p.) and systemic therapy (B16 lung metastases and L10A s.c. tumors) with bryostatin were successful at prolonging survival time. Multiple i.p. doses of bryostatin at a minimum level of 0.5-1.0 microgram/injection were required to observe significant in vivo antitumor effects. The success of in vivo administration of bryostatin in mice bearing 8-10-mm s.c. masses of L10A lymphoma (5-10 x 10(9)) and our further observation that five of a panel of six human B-cell lymphoma cell lines were sensitive to the growth inhibitory effects of bryostatin in vitro suggest that bryostatin may be effective in treating lymphoid malignancies in humans.
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Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Lactonas/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Animais , Briostatinas , Resistência a Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Macrolídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The investigational chemotherapeutic drug flavone acetic acid (FAA) acts as an immunomodulator by augmenting natural killer activity in both humans and rodents after in vivo administration. The accumulated data derived from a series of experiments also demonstrates that FAA synergizes with interleukin 2 (IL-2) for the treatment of murine renal cancer. The immunomodulatory and immunotherapeutic effects of FAA are strictly dose dependent with doses of FAA greater than 150 mg/kg effectively synergizing with IL-2, and doses less than 150 mg/kg exhibiting very little therapeutic effect. The antitumor and immunomodulatory effects of FAA are more pronounced in vivo than in vitro. Collectively, these results suggested that cytokines induced by FAA may contribute to these effects, and that the induction of such cytokines may also be very dose dependent. Studies were therefore initiated to investigate whether the in vivo administration of FAA would alter the expression of cytokine mRNA in leukocytes. Splenic leukocytes or liver nonparenchymal cells from untreated and FAA-treated mice were used as a source of RNA for Northern blot analysis. Interferon alpha and interferon gamma mRNA in the spleen was upregulated within 1.5 h after FAA administration, with peak induction occurring by about 2 h. An upregulation of tumor necrosis factor alpha mRNA was detected in the spleen by 0.5-1 h after treatment with peak induction occurring by 1-1.5 h. Induction of tumor necrosis factor alpha mRNA was also detected in hepatic nonparenchymal cells. No up-regulation of splenic mRNA for tumor necrosis factor beta, IL-1 alpha or beta, or IL-2 was detected after FAA administration. IFN and TNF activities were detectable in the serum by bioassay immediately following the appearance of mRNA in FAA mice. The observed up-regulation by FAA of cytokine mRNA and the corresponding serum protein was strictly dose dependent with substantial induction of both mRNA and proteins occurring only at FAA doses greater than or equal to 150 mg/kg, a dose range also shown to be the minimum required for immunomodulatory and immunotherapeutic effects. In summary, these results demonstrate that FAA acts as a potent inducer of at least three cytokines in vivo, and suggest that the immunomodulatory and immunotherapeutic effects of FAA may be partially mediated by these induced cytokines.
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Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Fatores Biológicos/genética , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Animais , Linhagem Celular , Citocinas , DNA/genética , Relação Dose-Resposta a Droga , Flavonoides/uso terapêutico , Interferon Tipo I/genética , Interleucina-2/uso terapêutico , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Hibridização de Ácido Nucleico , RNA/genética , Proteínas Recombinantes/uso terapêutico , Fator de Necrose Tumoral alfa/genéticaRESUMO
Flavone acetic acid (FAA) is an investigational drug that augments natural killer activity, induces the genes for alpha- and gamma-interferon (IFN) and tumor necrosis factor alpha, and synergizes with recombinant interleukin 2 for the successful treatment of murine renal cancer. However, in most clinical studies of FAA only minimal immunomodulatory effects have been reported. Most of the patients in these studies have also been given sodium bicarbonate to prevent possible nephrotoxicity. The current study was performed to determine whether alkalinization had any effects on FAA-induced immune modulation and therapeutic activity in mice. The results showed that alkalinization inhibited the treatment of murine renal cancer by FAA plus recombinant interleukin 2 such that the survival rate of 84% in nonalkalinized mice was reduced to 0 in mice that were alkalinized during treatment. Alkalinization also significantly inhibited the ability of FAA to augment both splenic and hepatic natural killer activity in a dose-dependent manner. In contrast, alkalinization did not inhibit the ability of polyinosinic:polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose, maleic anhydride divinyl ether, or Propionibacterium acnes to augment liver-associated natural killer activity. By Northern blot analysis, it was shown that the induction of mRNA for IFN-alpha, IFN-gamma, and tumor necrosis factor alpha by FAA in the spleen cells of mice was significantly reduced in alkalinized mice. Consistent with a reduction in the FAA-induced expression of the cytokine genes, alkalinization also resulted in a significant decrease in both the peak serum concentration and duration of detectable IFN activity following FAA treatment. Increasing the dose of FAA in alkalinized mice to 300 mg/kg overcame the deleterious effects of alkalinization for treatment of murine renal cancer by FAA plus recombinant interleukin 2. These results demonstrate that the process of alkalinization inhibits the immunomodulatory and immunotherapeutic effects of FAA in mice and suggest that alkalinization might have similar deleterious effects on FAA-induced immune stimulation in human clinical trials.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Citocinas/genética , Flavonoides/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Interleucina-2/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Células Matadoras Naturais/imunologia , Animais , Citotoxicidade Imunológica/efeitos dos fármacos , Sinergismo Farmacológico , Flavonoides/farmacologia , Concentração de Íons de Hidrogênio , Células Matadoras Naturais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/uso terapêuticoRESUMO
Moderate antenatal renal pelvic dilation (5-15 mm) may suggest vesicoureteric reflux, but it is not known to predict renal scarring. Dimercaptosuccinic acid scans on such children aged over 4 years showed a scarring rate (0/133 boys, 1/56 girls) similar to our local population. Investigation and treatment of moderate dilation may not be required.
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Cicatriz/etiologia , Nefropatias/etiologia , Pelve Renal/patologia , Adolescente , Criança , Pré-Escolar , Cicatriz/diagnóstico por imagem , Dilatação Patológica/complicações , Dilatação Patológica/diagnóstico por imagem , Feminino , Doenças Fetais/diagnóstico por imagem , Humanos , Nefropatias/diagnóstico por imagem , Pelve Renal/diagnóstico por imagem , Masculino , Gravidez , Prognóstico , Cintilografia , Ácido Dimercaptossuccínico Tecnécio Tc 99m , Ultrassonografia Pré-Natal , Infecções Urinárias/etiologiaRESUMO
BACKGROUND: Studies to date on the prevalence of erectile dysfunction (ED) report varying results. The present study investigates the frequency and degree of ED, its determining factors as well as the help-seeking behavior of the patients. PATIENTS AND METHODS: A random sample of 628 Swiss men (mean age: 61.5 years) were examined by questionnaire regarding their sexual functioning, comorbidity, and help-seeking behavior. RESULTS: Of the respondents, 9.6% reported complete, 18.0% moderate, and 41.4% minimal ED. All grades of the disorder increased with age and correlated with somatic and psychiatric comorbidity as well as with drug intake. Only 3.2% reported having used drugs for improvement of erectile functioning. CONCLUSION: Only a small number of men suffering from ED seek the help of a doctor. Considering the efficacy of PDE5 inhibitors, objective information and competent medical counseling of ED patients are indicated.
Assuntos
Atitude Frente a Saúde , Disfunção Erétil/epidemiologia , Disfunção Erétil/psicologia , Comportamentos Relacionados com a Saúde , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Qualidade de Vida , Medição de Risco/métodos , Adulto , Comorbidade , Disfunção Erétil/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estresse Psicológico/epidemiologia , Suíça/epidemiologiaRESUMO
Introduction: The majority of physicians consider administrative tasks to be a burden. The present questionnaire is intended to clarify the expense of time for documentation tasks in the treatment of inpatients in a gynaecological department of a Swiss hospital and to what extent differences occur between senior physicians and junior physicians. Materials and Methods: For three weeks physicians in the gynaecological department of a central Swiss hospital documented minute for minute predefined tasks during their duty periods. A questionnaire in tabular form served as survey instrument for this working time analysis. The minute for minute details for the individual participants were summed for each clinical task listed in the questionnaire in order to subsequently calculate the amounts of time spent for the respective task categories and to subject them to a subgroup analysis. Results: The participation rate of the physicians amounted to 87â%. 287 questionnaires were included in the evaluation. According to the responses, 25â% of the clinical working time for inpatients was used for documentation of clinical tasks. The subgroup analysis revealed a higher proportion for assistant physicians (30â%) than for senior physicians (18â%). Discussion: The present working time analysis reveals an unfavourable ratio between surgical and administrative tasks between junior and senior physicians. In addition there is a danger that the true burden for junior physicians is underestimated by their superiors due to hierarchal differences.
RESUMO
To our knowledge, there have been no published comparisons of different techniques for measuring blood pressure during clinical trials. We undertook a comparison during clinical trials with verapamil and prazosin. During an open trial of verapamil we compared the treatment-induced blood pressure reductions as measured by clinic, intra-arterial, and self-recorded methods. The mean reduction in blood pressure was 38 +/- 13.6/20 +/- 10.1 mm Hg for clinic blood pressure, 24 +/- 17.9/16 +/- 7.3 mm Hg for self-recorded blood pressure, and 23 +/- 12.3/19 +/- 10.1 mm Hg for mean daytime intra-arterial blood pressure. During prazosin treatment the mean reduction in blood pressure was 28 +/- 21.5/18 +/- 8.5 mm Hg for clinic blood pressure, 21 +/- 20.5/6 +/- 13.7 mm Hg for self-recorded blood pressure, and 18 +/- 19.2/5 +/- 9.6 mm Hg for mean daytime intra-arterial blood pressure. There was little agreement between methods within individual patients and for group comparisons of intra-arterial or clinic methods. There was, however, good agreement between intra-arterial and self-recorded methods. This study suggests that self-recorded blood pressure recording is suitable for monitoring efficacy of antihypertensive agents in a group of patients, although caution must be exercised when interpreting the effects of therapy when measured by indirect methods in an individual patient.