RESUMO
Previous research has shown that childhood body size is associated with blood pressure in adulthood, and that early and rapid growth rates are correlated with adverse cardiovascular outcomes. Our objectives are to estimate associations between childhood body size growth parameters and adult blood pressure, and to examine the effect of early attainment of critical growth milestones on adult blood pressure, relative to normal or late attainment. Lifetime height and body mass index (BMI) measurements in childhood, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in adulthood are taken from participants in the Fels Longitudinal Study. Childhood growth curves are estimated separately for stature and BMI using the Preece-Baines and third-degree polynomial models, respectively. Associations between the resulting parameter estimates and adult blood pressure are then examined using linear mixed models. Our findings show that the ages of achievement of the stature-based growth onset and peak velocity, as well as the age of achievement of the BMI-based adiposity rebound, are negatively associated with adult blood pressure, implying that early height or BMI growth can lead to increased blood pressure in adulthood. There were subtle differences in these relationships based on age and gender, and also between SBP and DBP. These results expand on the existing literature, showing that not only childhood body size, but also the timing of childhood growth can have a deleterious effect on adult cardiovascular health.
Assuntos
Adiposidade , Pressão Sanguínea/fisiologia , Estatura , Índice de Massa Corporal , Adolescente , Adulto , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , MasculinoRESUMO
Lactic acid bacteria are symbiotic bacteria that naturally reside in the gastrointestinal tract of honey bees. They serve a multitude of functions and are considered beneficial and completely harmless. In our experiments Lactobacillus plantarum strain B35, isolated from honey bee digestive tract, was modified using pAD43-25 plasmid carrying a functional GFP gene sequence (gfpmut3a) and used as a model for monitoring and optimisation of the mode of application. The establishment of this strain in honey bee digestive tract was monitored using GFP fluorescence. Three different modes of oral application of this strain were tested: water suspension of lyophilised bacteria, aerosol application of these bacteria and consumption of sugar honey paste containing the lyophilised lactobacilli. Two days after administration the L. plantarum B35-gfp was present throughout the honey bee digestive tract with 104-105 cfu/bee with highest count observed for aerosol application.
Assuntos
Abelhas/microbiologia , Trato Gastrointestinal/microbiologia , Proteínas de Fluorescência Verde/genética , Lactobacillus plantarum/crescimento & desenvolvimento , Lactobacillus plantarum/genética , Animais , Fluorescência , Microbioma Gastrointestinal/fisiologia , Lactobacillus plantarum/isolamento & purificação , Plasmídeos/genética , Simbiose/fisiologiaRESUMO
Upstream neutral modes, counter propagating to charge modes and carrying energy without net charge, had been predicted to exist in some of the fractional quantum Hall states and were recently observed via noise measurements. Understanding such modes will assist in identifying the wavefunction of these states, as well as shedding light on the role of Coulomb interactions within edge modes. Here, operating mainly in the ν=2/3 state, we place a quantum dot a few micrometres upstream of an ohmic contact, which serves as a 'neutral modes source'. We show that the neutral modes heat the input of the dot, causing a net thermo-electric current to flow through it. Heating of the electrons leads to a decay of the neutral mode, manifested in the vanishing of the thermo-electric current at T>110 mK. This set-up provides a straightforward method to investigate upstream neutral modes without turning to the more cumbersome noise measurements.
RESUMO
Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.
Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/cirurgia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento , Doadores não RelacionadosRESUMO
Fractionally charged quasiparticles, which obey non-abelian statistics, were predicted to exist in the ν=8/3, ν=5/2, and ν=7/3 fractional quantum Hall states (in the second Landau level). Here we present measurements of charge and neutral modes in these states. For both ν=7/3 and ν=8/3 states, we found a quasiparticle charge e=1/3 and an upstream neutral mode only in ν=8/3-excluding the possibility of non-abelian Read-Rezayi states and supporting Laughlin-like states. The absence of an upstream neutral mode in the ν=7/3 state also proves that edge reconstruction was not present in the ν=7/3 state, suggesting its absence also in ν=5/2 state, and thus may provide further support for the non-abelian anti-pfaffian nature of the ν=5/2 state.
RESUMO
The analysis of repeated measure or clustered data is often complicated by the presence of correlation. Further complications arise for discrete responses, where the marginal probability-dependent Fréchet bounds impose feasibility limits on the correlation that are often more restrictive than the positive definite range. Some popular statistical methods, such as generalized estimating equations (GEE), ignore these bounds, and as such can generate erroneous estimates and lead to incorrect inferential results. In this paper, we discuss two alternative strategies: (i) using QIC to select a data-driven correlation value within the Fréchet bounds, and (ii) the use of likelihood-based latent variable modeling, such as multivariate probit, to get around the problem all together. We provide two examples of the repercussions of incorrectly using existing GEE software in the presence of correlated binary responses.
Assuntos
Interpretação Estatística de Dados , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Análise por Conglomerados , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Promoção da Saúde/métodos , Humanos , Funções Verossimilhança , Estudos Longitudinais , Análise Multivariada , Probabilidade , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Resultado do TratamentoRESUMO
Lead increasingly contributes to pollution of the environment and may play a role in the development of adverse effects in the human and animal body. Data concerning its mutagenic, clastogenic, and carcinogenic properties have been conflicting. In this study, we evaluated the frequency of micronuclei in bone marrow erythrocytes of rats treated with lead acetate trihydrate. Outbred Wistar rats were exposed to a daily dose of 100 mg/L drinking water for 125 days. The mean value of the total number of micronuclei observed in polychromatic erythrocytes of female rats was significantly higher than that found in the control group (13.375 +/- 2.722 against 9.625 +/- 3.204 micronuclei/1000 cells; P = 0.024 in ANOVA). In exposed female animals, no significant reduction of the ratio of polychromatic to normochromatic erythrocytes was observed (0.990 +/- 0.228 against 1.208 +/- 0.195; P = 0.060 in ANOVA). The effects of lead acetate trihydrate in male rats are both cytotoxic and genotoxic because of a decrease in ratio of polychromatic to normochromatic erythrocytes (0.715 +/- 0.431 against 1.343 +/- 0.306; P = 0.023, ANOVA followed by Tukey test) and an increase in frequency of micronucleated polychromatic erythrocytes (24.167 +/- 7.859 against 4.0 +/- 4.528 micronuclei/1000 cells; P < or = 0.001, ANOVA followed by Tukey test), respectively.
Assuntos
Núcleo Celular/patologia , Eritroblastos/patologia , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Compostos Organometálicos/toxicidade , Análise de Variância , Animais , Feminino , Masculino , Testes para Micronúcleos , Compostos Organometálicos/administração & dosagem , Ratos , Ratos WistarRESUMO
OBJECTIVE: Vildagliptin is a potent and selective dipeptidyl peptidase-IV (DPP-4) inhibitor that improves glycemic control in patients with type 2 diabetes mellitus by increasing alpha- and beta-cell responsiveness to glucose. This study investigated the pharmacokinetics of vildagliptin in patients with hepatic impairment compared with healthy subjects. METHODS: This was an open-label, parallel-group study in patients with mild (n = 6), moderate (n = 6) or severe (n = 4) hepatic impairment and healthy subjects (n = 6). All subjects received a single 100-mg oral dose of vildagliptin, and plasma concentrations of vildagliptin and its main pharmacologically inactive metabolite LAY151 were measured up to 36 h post-dose. RESULTS: Exposure to vildagliptin (AUC(0-infinity) and C(max)) decreased non-significantly by 20 and 30%, respectively, in patients with mild hepatic impairment [geometric mean ratio (90% CI): AUC(0-infinity), 0.80 (0.60, 1.06), p = 0.192; C(max), 0.70 (0.46, 1.05), p = 0.149]. Exposure to vildagliptin was also decreased non-significantly in patients with moderate hepatic impairment [-8% for AUC(0-infinity), geometric mean ratio (90% CI): 0.92 (0.69, 1.23), p = 0.630; -23% for C(max), geometric mean ratio (90% CI): 0.77 (0.51, 1.17), p = 0.293]. In patients with severe hepatic impairment, C(max) was 6% lower than that in healthy subjects [geometric mean ratio (90% CI): 0.94 (0.59, 1.49), p = 0.285], whereas AUC(0-infinity) was increased by 22% [geometric mean ratio (90% CI): 1.22 (0.89, 1.68), p = 0.816). Across the hepatic impairment groups, LAY151 AUC(0-infinity) and C(max) were increased by 29-84% and 24-63%, respectively, compared with healthy subjects. The single 100-mg oral dose of vildagliptin was well tolerated by patients with hepatic impairment. CONCLUSIONS: There was no significant difference in exposure to vildagliptin in patients with mild, moderate or severe hepatic impairment; therefore, no dose adjustment of vildagliptin is necessary in patients with hepatic impairment.
Assuntos
Adamantano/análogos & derivados , Inibidores da Dipeptidil Peptidase IV , Hipoglicemiantes/farmacocinética , Hepatopatias/metabolismo , Nitrilas/farmacocinética , Pirrolidinas/farmacocinética , Adamantano/administração & dosagem , Adamantano/efeitos adversos , Adamantano/farmacocinética , Adulto , Análise de Variância , Área Sob a Curva , Doença Crônica , Dipeptidil Peptidase 4 , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , VildagliptinaRESUMO
OBJECTIVES: To establish the relationship between nasal patency and the nitric oxide (NO) concentration in the nasal airways. METHODS: Unilateral nasal NO concentration (n = 11) and inhaled nasal NO concentration at oropharynx (n = 9) were measured in healthy adult volunteers. Subjects breathed normally through the nose with a known resistance (ranged from none to total occlusion) placed in one nostril. In a subgroup (n = 7), the unilateral nasal NO concentrations were determined with nasal cavity congestion induced by lateral decubitus. RESULTS: When the added nasal resistance was less than 6 cm H(2)0 per liter per second, the peak NO concentrations in the nose remained below 80 parts per billion (ppb). Thereafter, the higher the resistance, the greater the NO concentration. It was up to 1109.7 ppb when the front nostril was totally occluded. There was no correlation between oropharyngeal NO concentrations and resistance in the front of the nose (r = 0.4). There was a significantly negative correlation between nasal cavity volumes and nasal NO concentrations (r = -0.8, P <.001). CONCLUSIONS: Increases in nasal resistance to levels encountered in the nasal cycle and in recumbency augments the NO concentration within the obstructed side of the nose. Although that within the nose changes with patency, the NO concentration is constant down to the lower airways. The modulation role of the upper airways to the inhaled NO concentration remains unclear.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Homeostase/fisiologia , Cavidade Nasal/fisiopatologia , Obstrução Nasal/metabolismo , Obstrução Nasal/fisiopatologia , Óxido Nítrico/análise , Óxido Nítrico/fisiologia , Adulto , Análise de Variância , Testes Respiratórios , Feminino , Humanos , Medições Luminescentes , Masculino , Manometria , Pessoa de Meia-Idade , Obstrução Nasal/diagnóstico , Pletismografia Total , Decúbito DorsalRESUMO
Hypernephroma is one of the most common tumours to spread by extranodal metastases to the head and neck. We herein report on six patients with unusual metastatic hypernephroma to the head and neck area. In two of the six cases, the metastatic tumour in the head and neck was the presenting symptom, and the renal tumour was secondarily detected. Metastatic hypernephroma to the head and neck area has been demonstrated mostly in the paranasal sinuses, parotid gland, and the mandible. Among the six cases presented, four belong to the above-mentioned group, but the other two are rather rare cases, one metastatic to the nasopharynx and soft palate and the other to both lobes of the thyroid gland. Hypernephroma should be sought and excluded whenever a metastatic lesion is encountered in the head and neck area, even if the metastatic lesion is the first clinical presentation. The diagnosis of metastatic hypernephroma should be suspected in any patient with even a remote history of renal cell carcinoma.
Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias Renais/patologia , Adulto , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Terapia Combinada , Evolução Fatal , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias Renais/terapia , Masculino , Resultado do TratamentoRESUMO
AIMS: The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. METHODS: Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. RESULTS: Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow-up. Both pegylated and nonpegylated interferon-alpha2b were rapidly absorbed, with maximal concentrations occurring approximately 8 to 12 hours after dose administration. Pegylated interferon-alpha2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon-alpha2b concentrations declined rapidly. Volume of distribution for both compounds was similar (approximately 1 L/kg). Pegylated interferon-alpha2b elimination half-life was approximately 10-fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon-alpha2b. CONCLUSIONS: Pegylated and nonpegylated interferon-alpha2b safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.
Assuntos
Antivirais/farmacocinética , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/farmacocinética , Interferon-alfa/uso terapêutico , Absorção , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/química , Área Sob a Curva , Química Farmacêutica , Relação Dose-Resposta a Droga , Feminino , Hepatite C Crônica/sangue , Humanos , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/química , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Proteínas Recombinantes , Resultado do TratamentoRESUMO
Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.
Assuntos
Plaquetas/efeitos dos fármacos , Interleucina-10/farmacologia , Trombocitopenia/imunologia , Adulto , Contagem de Células , Método Duplo-Cego , Feminino , Hemoglobinas/análise , Humanos , Masculino , Megacariócitos/patologia , Contagem de Plaquetas , Proteínas Recombinantes/farmacologia , Baço/fisiopatologia , Estatísticas não Paramétricas , Trombocitopenia/sangueRESUMO
The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20-68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open-label, randomized, active controlled study. Patients received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for 24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg orally daily. Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related reductions in white cells, neutrophils and platelets. Addition of ribavirin reduced hemoglobin levels in a dose-related manner, did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count, and increased platelet counts. Neutrophil function tests (C5a and FMLP migration, killing curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in all dose groups. Anti-HCV activity, as measured by loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy. There was no evidence of pharmacokinetic interactions with either drug. We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were numerically superior to those obtained with PEG-Intron monotherapy.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Contagem de Células Sanguíneas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversos , Ribavirina/uso terapêuticoRESUMO
Recombinant human interleukin-10 (rhIL-10) is a potent and specific immunomodulatory agent which inhibits endotoxin-stimulated pro-inflammatory cytokine production by monocytes, blocks T-lymphocyte activation by antigen presenting cells, and modulates T(H)1/T(H)2 balance in immune responses. In previous clinical trials, rhIL-10 administered to healthy volunteers induced rapid and transient elevations of neutrophil and monocyte counts and reductions of lymphocyte counts in addition to suppression of endotoxin-stimulated whole blood cytokine synthesis. We sought to better characterize the effects of rhIL-10 on immunophenotypically defined subsets of circulating leukocytes that could be relevant to its immunomodulatory effects. Healthy volunteers were given single doses of 10 microg/kg rhIL-10 (n = 8) or equivalent placebo (n = 4) by intravenous injection. Significant changes of circulating leukocytes included transiently increased neutrophils and monocytes with parallel increases of CD33+ and CD14+ cells. Total lymphocytes as well as total CD3+, CD3+/CD4+ and CD3+/CD8+ cells transiently decreased. Mean fluorescence intensity of CD11a (integrin alpha-chain subunit of lymphocyte function antigen-1, LFA-1) on lymphocytes transiently but significantly decreased, suggesting a mechanism for transient alteration of lymphocyte trafficking. In addition, mean fluorescence intensity of HLA-DR (major histocompatibility class II) on CD14+ cells (predominantly monocytes) transiently but significantly decreased, implying a possible alteration of antigen presenting function. Further study will be required to elucidate the immunomodulatory roles and potential clinical significance of these hematologic changes in therapeutic trials of rhIL-10 in patients with chronic inflammatory and autoimmune diseases.
Assuntos
Interleucina-10/farmacologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Adulto , Antígenos de Superfície/sangue , Antígenos de Superfície/imunologia , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/sangue , Método Duplo-Cego , Antígenos de Histocompatibilidade Classe II/biossíntese , Antígenos de Histocompatibilidade Classe II/sangue , Humanos , Imunofenotipagem , Injeções Intravenosas , Interleucina-10/farmacocinética , Leucócitos/classificação , Antígeno-1 Associado à Função Linfocitária/biossíntese , Antígeno-1 Associado à Função Linfocitária/sangue , Placebos , Proteínas Recombinantes/farmacocinéticaRESUMO
It has been suggested that due to fatty infiltration, obstructive sleep apnea (OSA) patients have a narrower pharyngeal airway than normal persons. To identify potential fatty infiltration of pharyngeal tissues that may contribute to OSA, a histologic study of the distal soft palate was performed. Histologic sections of 46 oropharyngeal specimens were evaluated. This included 25 overweight OSA patients (25/31), 6 normal-weight OSA patients (6/31), and a control group of 15 healthy (non-OSA) individuals. A semiquantitative analysis of the fatty tissue was performed. In all 31 OSA patients an excess of fatty infiltration was found in the histologic oropharyngeal specimens in comparison to the control group. No correlation was found between the pharyngeal fatty infiltration degree, the body mass index, and the apnea index. Irrespective of their body weight, in none of the patients without OSA was excessive fatty infiltration seen. It is suggested that excessive pharyngeal fatty infiltration plays a role in upper airway obstruction in OSA and that it can be associated with the development of apnea.
Assuntos
Tecido Adiposo/patologia , Faringe/patologia , Síndromes da Apneia do Sono/patologia , Adolescente , Idoso , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Palato Mole/patologiaRESUMO
Surgical removal of the soft palate in cases of neoplastic disease has a functionally detrimental effect on the patient, resulting in rhinolalia and nasal regurgitation. The authors describe their original surgical technique for repairing the lateral soft palate defect using a uvulopalatal flap. The flap is readily available and the procedure is single staged and without sequela. The aim of this reconstructive procedure is to obtain a diminished soft palate defect by primary surgery. In five patients who underwent a partial excision of the soft palate, the surgical defect was corrected at the time of initial surgery by a uvulopalatal flap. In this technique, the surface of the defect was diminished, postoperative rhinolalia and regurgitation were unremarkable, and sometimes an obturator was obviated. Using a local myomucosal flap, the procedure is simple, safe, and effective.
Assuntos
Carcinoma Adenoide Cístico/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Palatinas/cirurgia , Palato Mole/cirurgia , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Técnicas de SuturaRESUMO
We administered interferon-alpha2b (IFN-alpha2b) by continuous subcutaneous infusion (60,000 IU/h, or 10 million IU/week) over 3 months to 7 patients with chronic hepatitis C. All had previously responded, as assessed by normalization of transaminases to the same dose of IFN administered by intermittent injection over 6 months, but had relapsed after cessation of therapy. The continuous infusion was tolerated well at the site of infusion, and the systemic side effects were similar in type but were lesser in intensity than with intermittent dosage. Four of 7 subjects had normalization of transaminase at the end of week 12 of therapy. Serum HCV RNA and HCV by PCR decreased with treatment, and there was a prompt and sustained increase in serum beta2-microglobulin and of 2', 5' OAS activity. The level of the latter appeared to correlate with response of the transaminase. Serum IFN concentrations were low but detectable throughout therapy. After stopping IFN administration, the transaminases in responders increased again to pretreatment levels.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Administração Cutânea , Adulto , Antivirais/efeitos adversos , Feminino , Humanos , Infusões Parenterais , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Especificidade de Órgãos , Projetos Piloto , Proteínas RecombinantesRESUMO
Interleukin-10 inhibits T-lymphocyte activation and proliferation and lipopolysaccharide-induced monocyte production of proinflammatory cytokines. Fifty-four healthy volunteers received single doses of recombinant human interleukin-10 (1.0, 2.5, 5.0, 10, 25, or 50 micrograms/kg) or placebo by subcutaneous injection (randomized double-blind assignment). Clinical adverse events were infrequent at doses below 50 micrograms/kg (five of six subjects had mild flu-like syndrome). Mean serum interleukin-10 concentrations were dose related. The mean terminal-phase half-life ranged from 2.7 to 4.5 hours, and the apparent volume of distribution ranged from 0.70 to 1.35 L/kg. Hematologic changes included transient mild to moderate increases of neutrophil counts, decreases of lymphocyte counts, and a delayed decrease of platelet counts. Recombinant human interleukin-10 significantly suppressed production of the proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha by whole blood stimulated ex vivo with Escherichia coli lipopolysaccharide.
Assuntos
Interleucina-10/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Linfócitos T/efeitos dos fármacos , Adulto , Antígenos CD/metabolismo , Método Duplo-Cego , Escherichia coli , Feminino , Meia-Vida , Humanos , Injeções Subcutâneas , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/metabolismo , Interleucina-10/efeitos adversos , Interleucina-10/farmacocinética , Lipopolissacarídeos/farmacologia , Masculino , Receptores de Interleucina-1/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Segurança , Sialoglicoproteínas/metabolismo , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Spinal instability may be a cause of juxtafacet cyst formation and the pain and disability that occur after surgical excision of the cyst. To determine the role of instability, a retrospective review of charts identified 60 facet cysts in 56 patients treated over a 6-year period. Three patients developed an asynchronous cyst at the same level but on the opposite side of the previously resected cyst and one patient had a recurrent cyst in the same location. Forty-one cysts were present in patients with radiculopathy and 16 in patients with neurogenic claudication. Two patients presented with myelopathy and one had cauda equina syndrome. Thirty-six of the 60 cysts were located at L4-5, the most mobile segment. Fifteen patients had spondylolisthesis, of whom two experienced worsening spondylolisthesis postoperatively. Seven patients had scoliosis and 20 had systemic arthritis. Fifty-five cysts were resected via mesial facetectomy. Six of the patients undergoing this procedure had transverse process fusions at initial surgery for preoperative instability. Two others required fusion for post-operative instability and increased spondylolisthesis. Follow-up review was available in 95% of patients with an average duration of 12 months. Forty patients had excellent relief of symptoms, 12 had occasional back pain, and one patient did poorly. Flexion/extension views of the spine are recommended both pre- and postoperatively to identify the need for fusion in patients with juxtafacet cysts.
Assuntos
Cistos/cirurgia , Doenças da Medula Espinal/cirurgia , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças da Medula Espinal/patologiaRESUMO
Over the past 4 years, 7.4% of deaths caused by strangulation in Peoria County, Ill., involved children under 18 years of age. Clinical review of a consecutive series of 13 children treated from 1985 through 1994 revealed an incidence of 32 of 10,000 intensive care unit admissions with a 5.5:1 male bias. Accidental causes were seen in six children, with suicide or autoerotic causes prevalent in older children and adolescents. Five children had behavioral disorders before injury. The initial Glasgow Coma Scale score was 8 or below in seven children. Cervical roentgenograms in all patients and computed tomographic examinations performed in seven children were interpreted as normal. Seven children required ventilatory assistance, and four had pneumonia or acute lung injury. Intracranial pressure monitoring in three children failed to reveal sustained elevations of pressure. Serial changes in electroencephalograms in five patients paralleled improvements in their clinical examinations. Ten children were normal on follow-up; one adolescent reported mild neurologic sequelae and one adolescent showed severe disability. One adolescent died 2 days after injury. Comparison of this series with previous reports of 26 children indicated that the extent of the initial injury and effectiveness of resuscitation were major determinates for outcome. Pulmonary complications were common, whereas the development of elevated intracranial pressure indicated a poor prognosis and suggested the use of telemetry in children, with clinical evidence of severe injury. Continued awareness of preventative measures for accidental strangulation in infants and intentional hanging in children with behavioral disorders may reduce the incidence of these injuries.