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1.
Osteoporos Int ; 29(2): 329-337, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29110061

RESUMEN

The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score ≥ 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. INTRODUCTION: This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. METHODS: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. RESULTS: The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score ≥ 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. CONCLUSIONS: The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.


Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Cumplimiento de la Medicación/estadística & datos numéricos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Accidentes por Caídas/estadística & datos numéricos , Anciano , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Canadá/epidemiología , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Esquema de Medicación , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Enfermedades Gastrointestinales/epidemiología , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Estudios Prospectivos , Autoinforme
2.
Osteoporos Int ; 28(10): 2867-2876, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28643048

RESUMEN

The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. INTRODUCTION: The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. METHODS: MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. RESULTS: Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P ≤ 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. CONCLUSIONS: The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.


Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Osteoporosis Posmenopáusica/tratamiento farmacológico , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Canadá/epidemiología , Utilización de Medicamentos/estadística & datos numéricos , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/psicología , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/psicología , Estudios Prospectivos , Psicometría
3.
Osteoporos Int ; 27(3): 1227-1238, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26637321

RESUMEN

SUMMARY: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. INTRODUCTION: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. METHODS: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0-22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0-100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0-1; OPAQ-SV, score 0-100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. RESULTS: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1% of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, -0.43; OPSAT-Q, -5.68; EQ-5D, -0.04 (new users) and -0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, -4.17 (experienced users); emotional status, -4.28 (new users) and -5.68 (experienced users); back pain, -5.82 (new users) and -11.33 (experienced users), all P < 0.01. CONCLUSIONS: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms.


Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Cumplimiento de la Medicación/estadística & datos numéricos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Calidad de Vida , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Canadá/epidemiología , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Europa (Continente)/epidemiología , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/psicología , Recursos en Salud/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/psicología , Satisfacción del Paciente , Estudios Prospectivos , Psicometría
4.
Osteoporos Int ; 20(12): 1989-98, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19333676

RESUMEN

SUMMARY: Previous studies have found an association between acid suppressants and fracture risk. We assessed fracture risk in patients taking concomitant acid suppressant and bisphosphonates. Positive associations were observed for any hip and vertebral fracture. The effect size was modest; however, the significance lies in the widespread prescribing of acid suppressants. INTRODUCTION: Previous studies have found that acid-suppressive medication (ASM) is associated with an increased risk of fracture. Bisphosphonates can cause upper gastrointestinal problems, and patients may be prescribed ASM to minimise these effects. METHODS: A retrospective cohort study using the GPRD was conducted in patients aged 40 years and older starting proton pump inhibitors (PPI, N = 234,144), H(2) receptor antagonists (H(2)RA, N = 166,798) or bisphosphonates (N = 67,309). Fracture risk in current versus past use of ASM and concomitant use of bisphosphonate plus ASM versus bisphosphonate alone was compared using time-dependent Cox regression. RESULTS: In the 6 months before initiating bisphosphonate therapy, 20.1% of patients received a PPI and 7.5% an H(2)RA. Current PPI use was associated with an increased risk of any (adjusted relative rate (ARR) 1.15, 95% CI 1.10-1.20), hip (ARR 1.22, 95% CI 1.10-1.37), and vertebral fracture (ARR 1.40, 95% CI 1.11-1.78); and concomitant bisphosphonates and PPIs with an increased risk of any (ARR 1.08, 95% CI 1.01-1.16) and hip fracture (ARR 1.24, 95% CI 1.08-1.42). CONCLUSIONS: ASM is associated with an increased risk of fracture when taken alone or in combination with bisphosphonates. Given the frequency of coprescription of ASM and bisphosphonates, this issue requires further investigation.


Asunto(s)
Antiácidos/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Fracturas Óseas/inducido químicamente , Adulto , Anciano , Antiácidos/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Utilización de Medicamentos/estadística & datos numéricos , Métodos Epidemiológicos , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/prevención & control , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Reino Unido/epidemiología
5.
Metabolism ; 45(5): 645-51, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8622610

RESUMEN

Body wasting (cachexia) is a common feature of cancer and a major cause of morbidity and mortality. The mechanisms underlying cachexia are largely unknown, and studies in experimental animals have focused mainly on solid tumors. Therefore, the objective of the present study was to quantify and investigate cachexia in experimentally induced T-cell leukemia in the rat. Induction of leukemia by serial passage (injection of cervical lymph node suspension) resulted in a rapid increase in white blood cell (WBC count, hypertrophy of the spleen (by day 11), and severe morbidity within 17 to 18 days. Body weight gain and food intake declined steadily in leukemic animals from day 12, although weight loss was significantly greater in pair-fed, nonleukemic animals. However, leukemic rats had a lower body fat content and higher water content than pair-fed animals on day 18, so the measurement of body weight significantly underestimated the severity of cachexia. Resting oxygen consumption (VO2), measured during the light phase, declined in pair-fed animals from day 13, but was elevated in leukemic rats on days 12 to 18 by 25% (P < .05, one-way ANOVA) compared with pair-fed rats and by 7% (P < .05, one-way ANOVA) relative to free-feeding controls. Hypermetabolism was associated with an increase in brown adipose tissue (BAT) activity (74% and 89%, respectively, P < .05, one-way ANOVA) in leukemic rats compared with control and pair-fed groups. Effects of leukemia on VO2 and BAT were prevented by administration of the adrenergic antagonist, propranolol. These results indicate that T-cell leukemia in the rat results in rapid and severe cachexia, which is largely due to marked hypophagia, but is also accompanied by inappropriately high rates of energy expenditure that are mediated by sympathetic activation of BAT thermogenesis.


Asunto(s)
Caquexia/etiología , Leucemia de Células T/complicaciones , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Antagonistas Adrenérgicos beta/farmacología , Animales , Peso Corporal , Alimentos , Leucemia de Células T/fisiopatología , Masculino , Oxígeno/metabolismo , Propranolol/farmacología , Ratas
6.
Metabolism ; 46(4): 359-65, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9109835

RESUMEN

We have previously demonstrated that experimentally induced T-cell leukemia in the rat results in a rapid and severe cachexia. This weight loss is largely due to a reduction in food intake, but is also accompanied by inappropriately high rates of energy expenditure. Increases in resting oxygen consumption (VO2) of 25% to 35% above the levels of pair-fed animals were observed over the period of weight loss. The present study investigated the possible involvement of prostaglandins in the cachexia induced by T-cell leukemia in the rat. Acute systemic injection of the cyclo-oxygenase inhibitors (indomethacin 1 mg/kg or flurbiprofen 1 mg/kg intraperitoneally [IP]) significantly reduced (by 14% and 10%, respectively) the increase in metabolic rate and also reversed the elevated body temperature of leukemic animals. Intracerebroventricular (ICV) injection of indomethacin (0.2 mg/kg) had only modest effects on the increase in temperature or hypermetabolism of leukemic animals. Long-term daily injection of indomethacin or flurbiprofen (1 mg/kg/d IP) had no significant effect on food intake or body weight of leukemic animals, and neither treatment significantly affected disease status. Indomethacin significantly reduced the decline in epididymal fat pad weight of leukemic animals. These data indicate that prostaglandins, produced peripherally, are involved in the acute hypermetabolism associated with T-cell leukemia, but have little or no effect on the hypophagia or body weight loss of leukemic rats.


Asunto(s)
Caquexia/fisiopatología , Leucemia de Células T/fisiopatología , Prostaglandinas/fisiología , Animales , Regulación de la Temperatura Corporal , Peso Corporal/efectos de los fármacos , Caquexia/complicaciones , Caquexia/metabolismo , Conducta Alimentaria/efectos de los fármacos , Flurbiprofeno/farmacología , Indometacina/farmacología , Leucemia de Células T/complicaciones , Leucemia de Células T/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Oxígeno/metabolismo , Ratas
7.
J Appl Physiol (1985) ; 67(3): 1020-3, 1989 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2676949

RESUMEN

Increased energy expenditure often occurs during illness or after injection of endotoxin and can contribute to the generation of fever. In laboratory rats and mice the thermogenic response has been attributed to the sympathetic activation of brown adipose tissue (BAT), although mice often fail to show pyrexia. In this study the effects of malaria on O2 consumption and BAT were studied in mice inoculated with Plasmodium berghei. Parasitemia was maximal (greater than 50% of erythrocytes showing positive Leishman staining) 72 h after inoculation. Up to this time body weight and food intake were similar to values for control mice, although colonic temperatures were slightly depressed in infected mice. Thereafter, infected mice showed marked hypophagia, loss of body weight, and severe hypothermia; colonic temperature was less than 31 degrees C at 96 h when the experiment was terminated. Resting O2 consumption (VO2) measured at 24 degrees C was slightly elevated in infected mice 12 h after inoculation and reached a peak value (31% above controls) at 48 h. VO2 returned to the same value as controls at 96 h. In vitro thermogenic activity of BAT (assessed from binding of guanosine diphosphate to isolated mitochondria) was not significantly altered in infected mice. These data demonstrate a marked thermogenic response to malarial infection, but this is not accompanied by fever in mice and is dissociated from stimulation of BAT activity.


Asunto(s)
Tejido Adiposo Pardo/fisiopatología , Malaria/fisiopatología , Consumo de Oxígeno , Animales , Regulación de la Temperatura Corporal , Metabolismo Energético , Guanosina Difosfato/metabolismo , Masculino , Ratones , Mitocondrias/metabolismo , Plasmodium berghei
8.
J Appl Physiol (1985) ; 72(6): 2322-8, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1321111

RESUMEN

Fever and activation of acute phase responses were induced in human volunteers by intramuscular injection of typhoid vaccine. Vaccine injection caused a rapid (within 1 h) and sustained rise in metabolic rate (peak response 16%, 6-8 h), followed by later increases in white blood cell count (3-4 h), skin temperature (4-5 h), oral temperature (5-6 h), heart rate (6-8 h), and plasma cortisol (5-8 h). A peak fever [1.2 +/- 0.2 degree C (SE) rise] was recorded 12 h after vaccine injection. The involvement of the sympathetic nervous system in the development of these responses was investigated by the oral administration of propranolol before (80 mg) and 3 h after (40 mg) vaccine injection. Propranolol prevented the increases in metabolic rate, heart rate, and skin temperature but did not inhibit the rise in oral temperature or white cell count after vaccine administration. These data indicate that the sympathetic nervous system is responsible for the rise in energy expenditure associated with fever in humans. However, the rise in body temperature can develop in the absence of this increase in metabolic rate possibly by changes in heat loss.


Asunto(s)
Fiebre/etiología , Receptores Adrenérgicos beta/fisiología , Vacunas Tifoides-Paratifoides/efectos adversos , Reacción de Fase Aguda/etiología , Reacción de Fase Aguda/fisiopatología , Adolescente , Adulto , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Metabolismo/efectos de los fármacos , Propranolol/farmacología , Temperatura Cutánea/efectos de los fármacos
9.
Artículo en Inglés | MEDLINE | ID: mdl-8415812

RESUMEN

The thermogenic (increase in oxygen consumption, VO2) and pyrogenic (Tc) responses to the cytokine interleukin-1 beta (IL-1 beta) were studied in rats fed a n-3 fatty acid supplemented diet (8.75% n-3 fatty acids/kg diet). 4-6 weeks after commencing the diets, the n-3 supplemented rats exhibited reduced pyrogenic (0.5 +/- 0.1 degrees C versus 1.1 +/- 0.2 degrees C in control animals) and thermogenic (9 +/- 3% versus 22 +/- 6% in control animals) responses to intraperitoneal (i.p.) injection of IL-1 beta (1 micrograms/rat). However, responses to centrally administered IL-1 beta (5ng intracerebroventricular (i.c.v.)) were similar in both groups at this time. After 8-9 weeks of supplementation, n-3 supplemented animals exhibited attenuated responses to both ip IL-1 beta (VO2 responses reduced by 68% and Tc by 0.8 degrees C) and also i.c.v. IL-1 beta (VO2 responses reduced by 56% and Tc by 0.7 degrees C). N-3 supplementation did not, however, influence the thermogenic capacity of these animals since responses to noradrenaline were similar in control and n-3 fed animals (50% increase in VO2). These findings demonstrate that n-3 supplementation modifies the pyrogenic and thermogenic responses to IL-1 beta, probably via changes in eicosanoid metabolism. Modification of central responses to IL-1 are delayed compared to the effects of peripheral administration indicating separate mechanisms of IL-1 on fever and thermogenesis in the brain and the periphery.


Asunto(s)
Temperatura Corporal/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Interleucina-1/farmacología , Consumo de Oxígeno/efectos de los fármacos , Animales , Temperatura Corporal/fisiología , Ácidos Grasos Omega-3/administración & dosificación , Fiebre/fisiopatología , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Interleucina-1/administración & dosificación , Masculino , Consumo de Oxígeno/fisiología , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología
10.
Brain Res Bull ; 32(3): 223-6, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8374800

RESUMEN

Arachidonic acid [20:4(N-6)] has been implicated in neurological damage induced by cerebral ischaemia. Membrane arachidonate concentrations can be reduced by changes in dietary fat intake. Therefore, in the present study, we have investigated the effects of N-3 fatty acid supplementation on neuronal damage induced by permanent focal cerebral ischaemia or pharmacological activation of striatal NMDA receptors. Weanling rats were fed either a control diet or an N-3 supplemented diet (1.75% by weight as N-3 fatty acids) for 6 weeks. N-3-supplemented animals reduced ischaemic damage following middle cerebral artery occlusion (36%, p < 0.05), and excitotoxic damage induced by infusion of the selective NMDA agonist (1-aminocyclobutane-cis-1,3-dicarboxylic acid, 43%, p < 0.001) compared to the control-fed group. These data are consistent with the proposed role of arachidonic acid in ischaemic and excitotoxic brain damage, and suggest that modest dietary supplementation with N-3 fatty acids may offer benefit to populations at high risk of stroke.


Asunto(s)
Aminoácidos Cíclicos , Aminoácidos/toxicidad , Encéfalo/efectos de los fármacos , Grasas de la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Ataque Isquémico Transitorio/prevención & control , Neuronas/efectos de los fármacos , Neuronas/patología , Neurotoxinas/toxicidad , Animales , Encéfalo/patología , Cuerpo Estriado/efectos de los fármacos , Alimentos Fortificados , Infusiones Parenterales , Ataque Isquémico Transitorio/patología , Masculino , Ratas , Ratas Sprague-Dawley
11.
Eur Cytokine Netw ; 8(1): 45-9, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9110147

RESUMEN

The objective of this study was to investigate the involvement of cytokines (IL-1, IL-6 and TNF-alpha) in cachexia induced by T-cell leukaemia in the rat. Leukaemic rats exhibited a marked and significant increase in circulating IL-6 concentration from days 12-17 corresponding to the period of weight loss after induction of leukaemia. IL-6 plasma bioactivity correlated significantly with spleen weight and weight loss, implicating IL-6 in the cachectic response. In contrast, IL-1 and TNF-alpha plasma bioactivities were not increased compared to control rats, indicating that these cytokines are not circulating mediators of cachexia induced by T-cell leukaemia in the rat. These data suggest that IL-6 produced by the host may contribute to cachexia induced by T-cell leukaemia.


Asunto(s)
Caquexia/metabolismo , Interleucina-1/fisiología , Interleucina-6/fisiología , Leucemia de Células T/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , Animales , Caquexia/etiología , Interleucina-1/sangre , Interleucina-6/sangre , Leucemia de Células T/complicaciones , Masculino , Ratas
12.
Clin Nutr ; 12(6): 321-8, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16843333

RESUMEN

The effect of dietary fish oil supplementation on acute phase responses to intramuscular injection of typhoid vaccine, and in vitro cytokine production, was investigated in human volunteers. Half of the subjects supplemented their normal diet with 4.5 g/day of fish oil for 6-8 weeks. Injection of typhoid vaccine in unsupplemented subjects caused an increase in white cell count, resting heart rate, metabolic rate, oxygen consumption, and oral temperature. Fish oil supplementation inhibited the tachycardia and attenuated the maximal increases in oral temperature and metabolic rate following typhoid vaccine. However, interpretation of these latter results were complicated by similarly attenuated responses in saline-injected subjects. The in vitro production of interleukin-1 and interleukin-6 from whole blood was suppressed by fish oil supplementation, however, production of tumor necrosis factor alpha was not significantly altered. Fish oil supplementation may therefore provide a non-pharmacological approach of attenuating several of the responses associated with injury and infection and this may be related to reduced cytokine (IL-1 and IL-6) production.

13.
Life Sci ; 45(9): 843-7, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2770424

RESUMEN

The objective of this study was to assess whether bacterial infection stimulates oxygen consumption and brown adipose tissue (BAT) activity. Guinea pigs infected with Legionella pneumophila showed marked fever and a significant (33%) increase in resting oxygen consumption (VO2), 24h after infection. At this time, food intake and body weight were normal and the in vitro thermogenic activity of BAT taken from infected animals was elevated by 64% above that of control guinea pigs. VO2 and BAT activity fell to control values by 48h as infected animals became moribund and over this period food intake was markedly reduced.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Tejido Adiposo/metabolismo , Enfermedad de los Legionarios/metabolismo , Consumo de Oxígeno , Animales , Modelos Animales de Enfermedad , Ingestión de Líquidos , Ingestión de Alimentos , Femenino , Fiebre , Cobayas , Pérdida de Peso
14.
Int J Gynecol Cancer ; 17(4): 886-9, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17309665

RESUMEN

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.


Asunto(s)
Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Neoplasias Endometriales/cirugía , Recurrencia Local de Neoplasia/radioterapia , Terapia Recuperativa , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Factores de Riesgo , Resultado del Tratamiento
15.
Am J Physiol ; 261(6 Pt 1): E698-705, 1991 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1685068

RESUMEN

Inflammation and localized tissue injury were induced in rats by intramuscular injection of turpentine. This caused rapid and sustained (2-24 h) increases in colonic temperature (Tc; up by 2.5 degrees C) and oxygen consumption (VO2; up by 30%) as well as hypophagia (57%). The early responses (0-2 h) were attenuated by anesthesia, C-fiber deafferentation, peripheral but not central injection of a cyclooxygenase inhibitor, or central injection of a neutralizing antibody to corticotropin-releasing factor (CRF). In contrast, the later (18-20 h) changes in Tc and VO2 were unaffected by anesthesia, C-fiber deafferentation, or central injection of a CRF antibody but were inhibited by either peripheral or central administration of a cyclooxygenase inhibitor. beta-Adrenoceptor blockade reduced both phases of the response, and brown adipose tissue activity was significantly elevated from 4 to 24 h after turpentine injection. These data suggest that different mechanisms mediate the metabolic response to localized tissue injury, the early phase involving neural mechanisms characteristic of stress and inflammation, whereas the later phase appears to depend on humoral factors that are commonly associated with infection.


Asunto(s)
Fiebre/etiología , Inflamación/metabolismo , Antagonistas Adrenérgicos beta/farmacología , Análisis de Varianza , Animales , Anticuerpos , Capsaicina/farmacología , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Hormona Liberadora de Corticotropina/inmunología , Hormona Liberadora de Corticotropina/metabolismo , Desnervación , Ingestión de Alimentos/efectos de los fármacos , Fiebre/metabolismo , Flurbiprofeno/farmacología , Inyecciones Intramusculares , Cinética , Masculino , Consumo de Oxígeno/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/metabolismo , Propranolol/farmacología , Ratas , Ratas Endogámicas , Trementina
16.
Am J Physiol ; 277(4): H1326-37, 1999 10.
Artículo en Inglés | MEDLINE | ID: mdl-10516167

RESUMEN

Several lines of evidence indicate that hypoxia is a stimulus to vascular smooth muscle cell (VSMC) proliferation that occurs in pulmonary hypertension. The present study tested the hypothesis that low O(2) tension directly stimulates human VSMC proliferation by inducing them to produce interleukin (IL)-1, a potent autocrine growth factor for human VSMC. Human VSMC derived from pulmonary artery, aorta, or saphenous vein were incubated in either a normal in vitro O(2) environment (20% O(2)) or in chambers containing low (approximately 1%) or moderate (5%) O(2). Levels of IL-1alpha and IL-1beta mRNA increased in human VSMC after 24-48 h of incubation in low O(2) compared with levels in normoxic cells and then decreased upon subsequent reoxygenation. Levels of cell-associated IL-1alpha also increased progressively after 24-48 h in low O(2); however, detectable IL-1alpha was not released from the cells in the media. IL-1beta was detectable in cell lysates and supernatants; however, the levels were not affected by exposure to low O(2). mRNA encoding for tumor necrosis factor-alpha (TNF-alpha), a related cytokine and VSMC mitogen, was not detectable in human VSMC exposed to either low or 20% O(2). Proliferation of human VSMC was not stimulated during exposure to low O(2), despite the fact that cells remained responsive to the mitogenic effect of exogenous IL-1. Interestingly, however, exposure to 5% O(2) enhanced proliferation of human VSMC but did not induce IL-1alpha production. Inhibition of IL-1 binding to the type I IL-1 receptor by exogenous addition of IL-1-receptor antagonist (10 microgram/ml) did not attenuate the proliferation rates of human VSMC incubated in 20%, 5%, or low O(2) or in human VSMC that were reoxygenated after exposure to low O(2). These results demonstrate two direct and distinct effects of hypoxia on VSMC. Exposure to moderately low O(2) tension induces VSMC proliferation, independent of IL-1, whereas exposure to very low O(2) tension induces production of IL-1alpha.


Asunto(s)
Hipoxia/patología , Interleucina-1/biosíntesis , Músculo Liso Vascular/metabolismo , División Celular/efectos de los fármacos , Células Cultivadas , Expresión Génica/fisiología , Humanos , Interleucina-1/genética , Interleucina-1/fisiología , Membranas Intracelulares/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Oxígeno/administración & dosificación , Oxígeno/farmacología , Receptores de Interleucina-1/antagonistas & inhibidores , Receptores de Interleucina-1/fisiología
17.
Am J Physiol ; 276(3): H901-12, 1999 03.
Artículo en Inglés | MEDLINE | ID: mdl-10070073

RESUMEN

Vascular smooth muscle cell (VSMC) proliferation plays a critical role in the failure of vascular surgeries and contributes to the development of atherosclerotic lesions. Evidence that interleukin-1 (IL-1) is a mitogen for cultured VSMC has implicated its release by activated macrophages in the development of atherosclerosis. VSMC also produce IL-1, including the precursor form of IL-1alpha. However, it is not known whether IL-1alpha precursor is processed to mature IL-1alpha or released from VSMC, nor is it known whether either precursor or mature IL-1alpha functions as an autocrine growth factor. The goals of the present study were to establish whether proliferation is enhanced in human VSMC transfectants producing IL-1alpha constitutively at levels comparable to those produced after activation, and to determine which domains of IL-1alpha are important for its activity. Human VSMC were stably transfected with expression vectors directing constitutive expression of either full-length IL-1alpha precursor [IL-1alpha-(1-271)], its NH2-terminal domain [IL-1alpha-(1-112)], or mature IL-1alpha [IL-1alpha-(113-271)]. Both IL-1alpha-(1-271) and IL-1alpha-(113-271) stable transfectants produced moderate levels of IL-1alpha (0.2-1.0 ng/10(6) cells) and released low levels of IL-1alpha into the supernatant (<20 pg/ml). VSMC stably transfected with either IL-1alpha-(1-271) or IL-1alpha-(113-271) expression plasmids proliferated rapidly compared with nontransfected or vector-transfected VSMC and displayed a distinct morphology characterized by elongated, spindle-shaped cells. Stable transfection with IL-1alpha-(1-271) was somewhat more effective than transfection with IL-1alpha-(113-271). Interestingly, VSMC transfected with IL-1alpha-(113-271) expression plasmids also expressed IL-1alpha-(1-271) mRNA, suggesting that IL-1alpha-(113-271) activates an IL-1-induced IL-1 autocrine loop. In contrast, neither proliferation rates nor morphology was affected by stable transfection with IL-1alpha-(1-112) expression plasmids. Exogenous IL-1 receptor antagonist partially reversed the enhanced DNA synthesis in VSMC transfected with either IL-1alpha-(1-271) or IL-1alpha-(113-271) expression plasmids, suggesting that the pro-proliferative effect of VSMC-derived IL-1alpha is at least partially mediated by signaling via the type I IL-1 receptor. These results demonstrate that IL-1alpha precursor is an autocrine growth factor for human VSMC and further indicate that amino acids 113-271 play a crucial role in its actions.


Asunto(s)
Interleucina-1/metabolismo , Músculo Liso Vascular/citología , Precursores de Proteínas/metabolismo , Western Blotting , División Celular/efectos de los fármacos , División Celular/fisiología , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/genética , Interleucina-1/farmacología , Fragmentos de Péptidos/genética , Plásmidos/fisiología , Sialoglicoproteínas/farmacología , Factores de Tiempo , Distribución Tisular , Transfección
18.
Anaesthesia ; 44(12): 953-8, 1989 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2619016

RESUMEN

Fifty-three patients were admitted in a 5-year period to the intensive care unit as a result of a complication of an anaesthetic technique. These patients represented 1 in 1543 anaesthetics carried out in the District in the period and 2.0% of all admissions to the intensive care unit. The mortality rate was 17%. The complication was considered to be wholly or partially avoidable in 14 instances (26%). Five of these subjects died and two had a residual neurological deficit.


Asunto(s)
Anestesia/efectos adversos , Cuidados Críticos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anestesia/mortalidad , Periodo de Recuperación de la Anestesia , Anestesia Obstétrica/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Unidades de Cuidados Intensivos , Masculino , Auditoría Médica , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Embarazo , Estudios Prospectivos
19.
J Med Vet Mycol ; 25(2): 115-23, 1987 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3598823

RESUMEN

Of several media tested for their ability to induce asexual reproduction in confirmed or suspected isolates of Mortierella wolfii obtained from cattle in various geographical locations, only silage extract agar worked consistently and rapidly. Its use should provide a simple reliable culturing procedure to assist with identification of clinical isolates of this fungus. Temperature growth response curves and electrophoretic patterns of soluble protein extracts of these isolates with characteristic morphological features of M. wolfii indicate substantial variation amongst them.


Asunto(s)
Aborto Veterinario/microbiología , Enfermedades de los Bovinos/microbiología , Mucorales/aislamiento & purificación , Mucormicosis/veterinaria , Animales , Bovinos , Medios de Cultivo , Electroforesis en Gel de Poliacrilamida , Femenino , Proteínas Fúngicas/análisis , Microscopía Electrónica de Rastreo , Mucorales/análisis , Mucorales/fisiología , Mucorales/ultraestructura , Mucormicosis/microbiología , Embarazo , Esporas Fúngicas , Temperatura
20.
Scand J Rheumatol ; 22(5): 207-14, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8235489

RESUMEN

Serum samples from 149 patients with RA and other rheumatological diseases, and 57 non-arthritic controls have been assayed for IgE antibodies to the cartilage collagen types II, IX and XI in their native and denatured state. Using an improved ELISA technique together with antigen-binding inhibition studies to confirm specificity, 10 of the 149 (7%) patients showed IgE antibodies to human collagen type II and bovine collagen types II, IX or XI. Some patients responded to only one collagen type whereas others had IgE positive responses to two or all three collagen species. Most of the IgE responses detected were directed towards the denatured collagens. Those sera showing an IgE response to bovine type II collagen produced a similar response to the human equivalent, including two patients with SLE. None of 57 control subjects demonstrated IgE specificity for any of the cartilage collagens. Patients with IgE specificity for the cartilage collagens did not demonstrate IgM or IgA specificity for these antigens, but two of these patients showed IgG responses to type II and XI collagens. Whereas eight patients were exclusively IgE-positive for the cartilage collagens, others expressed specificities for IgG, IgM or IgA. It therefore appears that the specific autoimmune profile for each patient is often different from others, both in terms of the class of immunoglobulin expressed and the collagen antigens recognised. At present no correlations were observed between the IgE-positive patients and their clinical assessment and/or prognosis.


Asunto(s)
Especificidad de Anticuerpos/inmunología , Autoanticuerpos/sangre , Cartílago Articular/inmunología , Colágeno/inmunología , Inmunoglobulina E/sangre , Enfermedades Reumáticas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Reacciones Antígeno-Anticuerpo , Bovinos , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/sangre
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