ABSTRACT
Varios estudios epidemiológicos de la radiación ionizante y el cáncer de piel, han demostrado que la radiación causa cáncer de piel no melanoma, principalmente carcinoma basocelular. Poco se sabe sobre la dosis de radiación ionizante, que podría causar carcinoma de células escamosas. Todos los estudios disponibles muestran que el riesgo de cáncer de piel es mayor, cuando la exposición a la radiación se produce a edades más tempranas que en más avanzadas; las pruebas indican que el exceso de riesgo para este tipo de cáncer, tiene una duración de varios años después de la irradiación. Por lo tanto, los pacientes previamente tratados con radiaciones ionizantes requieren un seguimiento permanente, para identificar el carcinoma cutáneo en una etapa temprana.
Several epidemiologic studies of ionizing radiation and skin cancer have shown that radiation causes non melanoma skin cancer, mainly basal cell carcinoma. Little is known about the dose of ionizing radiation that could cause squamous cell carcinoma. All available studies show that skin cancer risk is greater from radiation exposure at young ages than at older ages and the evidence indicates that the excess risk of skin cancer lasts for several years following irradiation. Therefore patients previously treated with ionizing radiation require lifelong monitoring to identify skin cancer at an early stage.
ABSTRACT
Varios estudios epidemiológicos de la radiación ionizante y el cáncer de piel, han demostrado que la radiación causa cáncer de piel no melanoma, principalmente carcinoma basocelular. Poco se sabe sobre la dosis de radiación ionizante, que podría causar carcinoma de células escamosas. Todos los estudios disponibles muestran que el riesgo de cáncer de piel es mayor, cuando la exposición a la radiación se produce a edades más tempranas que en más avanzadas; las pruebas indican que el exceso de riesgo para este tipo de cáncer, tiene una duración de varios años después de la irradiación. Por lo tanto, los pacientes previamente tratados con radiaciones ionizantes requieren un seguimiento permanente, para identificar el carcinoma cutáneo en una etapa temprana.(AU)
Several epidemiologic studies of ionizing radiation and skin cancer have shown that radiation causes non melanoma skin cancer, mainly basal cell carcinoma. Little is known about the dose of ionizing radiation that could cause squamous cell carcinoma. All available studies show that skin cancer risk is greater from radiation exposure at young ages than at older ages and the evidence indicates that the excess risk of skin cancer lasts for several years following irradiation. Therefore patients previously treated with ionizing radiation require lifelong monitoring to identify skin cancer at an early stage.(AU)
ABSTRACT
AIMS: To identify the causes for the inhomogeneity of ventricular repolarization and increased QT dispersion in hypothyroid mice. METHODS: We studied the effects of 5-propyl-2-thiouracil-induced hypothyroidism on the ECG, action potential (AP) and current density of the repolarizing potassium currents I(to,fast), I(to,slow), I(K,slow) and I(ss) in enzymatically isolated myocytes from three different regions of mouse heart: right ventricle (RV), epicardium of the left ventricle (Epi-LV) and interventricular septum. K(+) currents were recorded with the patch-clamp technique. Membranes from isolated ventricular myocytes were extracted by centrifugation. Kv4.2, Kv4.3, KChIP and Na/Ca exchanger proteins were visualized by Western blot. RESULTS: The frequency or conduction velocity was not changed by hypothyroidism, but QTc was prolonged. Neither resting membrane potential nor AP amplitude was modified. The action potential duration (APD)(90) increased in the RV and Epi-LV, but not in the septum. Hypothyroid status has no effect either on I(to,slow), I(k,slow) or I(ss) in any of the regions analysed. However, I(to,fast) was significantly reduced in the Epi-LV and in the RV, whereas it was not altered in cells from the septum. Western blot analysis reveals a reduction in Kv4.2 and Kv4.3 protein levels in both the Epi-LV and the RV and an increase in Na/Ca exchanger. CONCLUSION: From these results we suggest that the regional differences in APD lengthening, and thus in repolarization inhomogeneity, induced by experimental hypothyroidism are at least partially explained by the uneven decrease in I(to,fast) and the differences in the relative contribution of the depolarization-activated outward currents to the repolarization process.
Subject(s)
Action Potentials/physiology , Heart Ventricles/physiopathology , Hypothyroidism/physiopathology , Muscle Cells/metabolism , Animals , Blotting, Western , Disease Models, Animal , Electrocardiography , Male , Mice , Mice, Inbred BALB C , Patch-Clamp Techniques , Potassium Channels, Voltage-Gated/metabolismABSTRACT
INTRODUCTION: Within the context of participatory action research (PAR), a 4-stage process was established with the general aim of promoting improvements in the care offered to families of patients in the Intensive Care Unit (ICU). The 4 stages consisted of a situational diagnosis, proposals for change, the design and implementation of the proposals, and an evaluation. This paper presents the first 2 stages. OBJECTIVES: To define the attention given to families of patients in the Intensive Care Unit. To reach a consensus on areas for action/intervention in the unit. MATERIALS AND METHOD: A qualitative methodology. DESIGN: PAR. Data-collection technique: 4 focus groups made up of 10 professionals, and consensus with support groups made up of 30 members. Content analysis was performed. The theoretical saturation point was reached. RESULTS: Two documents were drawn up: 1) A situational diagnosis, describing the current situation of the attention given to families and 2) 10 proposals for change, 5 of which were given priority. They were: a session to familiarize professionals with evidence concerning families of patients in the ICU and the handing out of informative leaflets, the improvement of (nurse-family and intra-team) informative procedures, more privacy for patients and a reduction in environmental noise, a training plan for professionals, and change in the visiting policy. CONCLUSION: By using consensus-based methodologies, strategies for change can be prioritized and designed, adapted to the context in which they will be applied.
Subject(s)
Critical Illness , Family , Adult , Consensus , Family/psychology , Humans , Intensive Care Units , Models, TheoreticalABSTRACT
An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality.
Subject(s)
Disease Outbreaks , Legionella pneumophila/isolation & purification , Legionnaires' Disease/epidemiology , Adult , Aged , Aged, 80 and over , Amplified Fragment Length Polymorphism Analysis , Animals , Antigens, Bacterial/analysis , Bacterial Typing Techniques , Communicable Disease Control , Demography , Electrophoresis, Gel, Pulsed-Field , Female , Genotype , Humans , Incidence , Legionella pneumophila/classification , Legionnaires' Disease/microbiology , Male , Middle Aged , Spain/epidemiology , Urine/microbiology , Water MicrobiologyABSTRACT
PURPOSE: Topiramate (TPM) is an antiepileptic agent, first licensed in the United Kingdom in 1994, that is used in the treatment of patients with refractory seizure disorders. TPM is a monosaccharide d-fructose derivate, with sulfamate function, and so far, few adverse side effects have been reported. METHODS: We describe three patients with epilepsy who were treated with TPM and developed hypohidrosis, heat and exercise intolerance, as well as fever. The sudomotor function was assessed after peripheral stimulation with pilocarpine iontophoresis. RESULTS: Sweat response was reduced in all three patients. Signs and symptoms ceased after drug suppression. CONCLUSIONS: This side effect associated with TPM, which has not been described previously, can be clinically significant during heat stress and exercise challenge.
Subject(s)
Anticonvulsants/adverse effects , Epilepsy/drug therapy , Fructose/analogs & derivatives , Fructose/adverse effects , Hypohidrosis/chemically induced , Adolescent , Anticonvulsants/therapeutic use , Child , Epilepsies, Partial/drug therapy , Fever/chemically induced , Fructose/therapeutic use , Humans , Hypohidrosis/diagnosis , Infant , Male , Spasms, Infantile/drug therapy , Sweating/drug effects , TopiramateABSTRACT
OBJECTIVE: To evaluate the characteristics of flutamide induced hepatotoxicity. MATERIAL AND METHODS: In this retrospective study we have analyzed all cases of flutamide hepatotoxicity submitted to the Andalucian Registry of drug-induced liver disease. Data were collected using a structured reporting form. Causality assessment was performed using two clinical scales: the standard CIOMS scale and the recently developed María and Victorino scale. RESULTS: Nine of 185 patients (4.9%) were identified. In 8 male patients, mean age 75 years (range 65-83), flutamide was indicated for palliative therapy of disseminated prostatic carcinoma, and in one young female (14 years) was given for the treatment of facial hirsutism. The mean duration of the flutamide therapy was 151 days (range 4-443). All patients presented with overt liver injury, the most frequent features being asthenia, anorexia, weight loss, nausea, vomiting and jaundice. No patient showed hypersensitivity features. In two patients (22%) the hepatic damage evolved to fulminant liver failure, one of them undergoing a liver transplantation and the other subsequently died. An additional patient died of a non-hepatic related cause when his liver function was improving. Causality assessment by the two clinical scales did not exclude any case, but the two patients who died where classified as unlikely by the María and Victorino scale. CONCLUSIONS: Flutamide can induce severe acute hepatitis, probably due to an idiosyncratic metabolic mechanism. Liver tests monitoring should probably be mandatory during the first months of flutamide therapy and the drug withdrawn if transaminases began to increase.
Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Chemical and Drug Induced Liver Injury , Flutamide/adverse effects , Liver/drug effects , Adolescent , Aged , Aged, 80 and over , Female , Hirsutism/drug therapy , Humans , Male , Prostatic Neoplasms/drug therapy , Retrospective StudiesABSTRACT
1. Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. 2. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. 3. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. 4. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 microM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. 5. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. 6. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels.
Subject(s)
Action Potentials/drug effects , Cnidarian Venoms/pharmacology , Heart/drug effects , Sea Anemones/chemistry , Sodium Channels/drug effects , Amino Acid Sequence , Animals , Cloning, Molecular , Cnidarian Venoms/isolation & purification , Dose-Response Relationship, Drug , Heart Ventricles/cytology , Heart Ventricles/drug effects , In Vitro Techniques , Models, Biological , Molecular Sequence Data , Patch-Clamp Techniques , Rats , Sequence Analysis, Protein , Sequence Homology, Amino Acid , Ventricular Function , Xenopus laevisABSTRACT
BACKGROUND: This study investigated the effects of intra-abdominal blood on the systemic response to peritonitis using a murine model of hemorrhage, peritonitis, and multiple organ dysfunction syndrome. METHODS: The model used male ICR mice subjected to hemorrhage and intraperitoneal zymosan. Half of the mice received intraperitoneal blood. Outcome measures included lung myeloperoxidase, lung edema, lung injury score, and plasma and lung tissue chemokine production. RESULTS: Peritoneal blood (in association with peritoneal inflammation) increased lung neutrophil sequestration (myeloperoxidase) (2.56 +/- 1.42 vs. 1.45 +/- 0.49 U/left lung, p = 0.04) and lung weight (0.11 +/- 0.04 vs. 0.07 +/- 0.02 g/left lung, p = 0.02), and was associated with significantly higher chemokine levels in plasma (KC and MCP-1) and lung tissue (KC, MIP-2, and MCP-1). Both plasma and lung tissue neutrophil chemoattractants KC and MIP-2 were significantly linearly correlated with myeloperoxidase (p < 0.009), and lung tissue KC (a neutrophil chemokine) and MCP-1 and MIP-1alpha (mononuclear cell chemokines) correlated with lung injury score (p < 0.003). CONCLUSION: Although blood alone in the peritoneal cavity was well tolerated, in conjunction with inflammation, it was synergistic in amplifying the systemic inflammatory response. The amplified lung injury in this model was associated with significant increases in circulating and lung tissue chemokine concentrations.
Subject(s)
Chemokines/blood , Cytokines/blood , Hemoperitoneum/immunology , Peritonitis/immunology , Systemic Inflammatory Response Syndrome/immunology , Animals , Leukocyte Count , Lung/immunology , Male , Mice , Mice, Inbred ICR , Multiple Organ Failure/immunology , Neutrophils/immunologyABSTRACT
In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.
Subject(s)
Heart/drug effects , Hydrochlorothiazide/pharmacology , Sodium Chloride Symporter Inhibitors/pharmacology , Action Potentials/drug effects , Animals , Calcium/metabolism , Diuretics , Dose-Response Relationship, Drug , Electrophysiology , Heart/physiology , Heart Conduction System/drug effects , Heart Conduction System/physiology , Heart Ventricles/drug effects , In Vitro Techniques , Membrane Potentials/drug effects , Muscle, Smooth/cytology , Muscle, Smooth/drug effects , Myocardial Contraction/drug effects , Myocardium/cytology , Patch-Clamp Techniques , Potassium Channels/drug effects , Rats , Sodium/metabolism , Stimulation, ChemicalABSTRACT
Objetivo: evaluar las características de la hepatotoxicidad por flutamida.Material y métodos: análisis de 9 casos de toxicidad hepática secundaria a este fármaco remitidos al Registro Andaluz de Hepatopatías asociadas a medicamentos. La información se recogió en un protocolo estructurado. La imputabilidad de la flutamida se estimó en cada uno de los casos por dos escalas diagnósticas; Council for International Organization of Medical Sciences (CIOMS) y una recientemente validada (María y Victorino).Resultados: 9 de 185 casos (4,9 por ciento) de hepatotoxicidad remitidos al registro eran debidos a flutamida. En 8 pacientes varones con edad media de 75 años (rango 65-83), la flutamida se indicó para la paliación del carcinoma de próstata metastásico, y en una mujer de 14 años para el tratamiento del hirsutismo facial. El tiempo medio de duración del tratamiento fue de 151 días (rango 4-433). El episodio de hepatotoxicidad tuvo expresión clínica en todos los pacientes, siendo las manifestaciones más frecuentes: astenia, anorexia, pérdida de peso, náuseas, vómitos e ictericia. Ningún paciente presentó manifestaciones de hipersensibilidad. Dos pacientes (22 por ciento) presentaron fallo hepático fulminante, falleciendo uno y realizándose transplante hepático en el otro. Un tercer paciente falleció cuando la lesión hepática estaba en fase de resolución. No hubo ningún caso excluido en la evaluación de im putabilidad, pero los dos casos de éxitus fueron clasificados como dudosos por la escala de María y Victorino. Conclusiones: flutamida puede producir hepatitis aguda grave, ocasionalmente fulminante, por un mecanismo presuntamente de idiosincrasia metabólica. Debería monitorizarse el perfil hepático durante los primeros meses de tratamiento con flutamida, suspendiéndose el fármaco en caso de detectarse alteraciones (AU)
Subject(s)
Adolescent , Aged, 80 and over , Aged , Male , Female , Humans , Antineoplastic Agents, Hormonal , Retrospective Studies , Hirsutism , Liver , Liver Diseases , Flutamide , Prostatic NeoplasmsABSTRACT
BACKGROUND: Recent studies have documented that the systemic inflammatory response syndrome (SIRS) score is a useful predictor of outcome in critical surgical illness. The duration and severity of SIRS are associated with posttrauma multiple organ dysfunction and mortality. We sought to determine whether the severity of SIRS at admission is an accurate predictor of mortality and length of stay (LOS) in trauma patients. METHODS: Prospective data of 4,887 trauma admissions to a Level I trauma center over a 18-month period (January 1997 to July 1998) were analyzed. Patients were stratified by age and Injury Severity Score (ISS), and a SIRS severity score (1 to 4) was calculated at admission (1 point for each component present: fever or hypothermia, tachypnea, tachycardia, and leukocytosis). The SIRS score was evaluated as an independent predictor of mortality and LOS by chi2 and multivariate logistic regression. RESULTS: Trauma patients (n = 4,887, 83% blunt injuries, 72% male) had the following characteristics: 73.1% were age 18 to 45 years, 17.5% were age 46 to 65 years, and 9.4% were age > or =66 years; 77.7% had ISS less than 15, 18.8% had ISS 16 to 29, and 3.5% had ISS greater than 29. Analysis of variance adjusting for age and ISS determined that SIRS score of 2 was a significant predictor of LOS. Furthermore, the relative risk of death increased significantly with SIRS score of 2 when age and ISS were held constant. CONCLUSION: Logistic regression analysis confirmed that a SIRS score of 2 was a significant independent predictor of increased mortality and LOS in trauma patients. These data suggest that admission SIRS scoring in trauma patients is a simple tool that may be used as a predictor of outcome and resource utilization.
Subject(s)
Severity of Illness Index , Systemic Inflammatory Response Syndrome/epidemiology , Wounds and Injuries/diagnosis , Adolescent , Adult , Aged , Baltimore/epidemiology , Female , Humans , Incidence , Length of Stay , Logistic Models , Male , Middle Aged , Prognosis , Prospective Studies , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology , Wounds and Injuries/complications , Wounds and Injuries/mortalityABSTRACT
Dysfunction of small fibers may appear in isolation or associated with large fiber lesions. In some acute neuropathies, such as pandysautonomia, small-fiber impairment is relatively pure but it may also appear in disorders with prominent somatic damage, such as Guillain-Barré syndrome, in which autonomic failure worsens the prognosis. At the present time, chronic idiopathic distal small-fiber neuropathy is diagnosed more frequently, and in some prevalent disorders, such as diabetic or amyloidotic polyneuropathies, small-fiber dysfunction is very noticeable. In pure autonomic failure, a peripheral autonomic failure exists, distinguishing it from multiple-system atrophy. Complex regional pain syndrome is a severe condition in which small fibers are responsible for disabling signs and symptoms, and only instrumental recordings lead to the proper treatment. Standard neurophysiological techniques evaluate large myelinated fibers exclusively. Small-fiber polyneuropathy has been considered as a type of somatic neuropathy, but thin myelinated and unmyelinated fibers are responsible not only for temperature and pain perception but also autonomic function. For instance, full autonomic evaluation is needed in some clinical situations such as autonomic failure in the elderly or orthostatic intolerance syndrome. To evaluate small-fiber impairment we need a battery of sensitive, reproducible, specific and noninvasive tests covering somatic and autonomic systems. In this review, we describe and analyze a number of neurophysiological techniques used to diagnose and characterize small-fiber dysfunction in humans. These include cardiovascular monitoring, sudomotor testing, pupillary responses and quantitative sensory tests, and also to some extent thermography and laser evoked potentials. The use of such techniques has proven useful not only for diagnosis, but also to guide adequate therapy and optimize follow-up.
Subject(s)
Nerve Fibers, Myelinated/physiology , Peripheral Nervous System Diseases/physiopathology , Electrophysiology , Evoked Potentials , Humans , Posture , Reflex , Sensory Receptor Cells , Sensory Thresholds , SweatingSubject(s)
Calcinosis/pathology , Stomach Diseases/pathology , Adult , Aluminum Hydroxide/adverse effects , Antacids/adverse effects , Calcinosis/chemically induced , Chronic Disease , Dyspepsia/complications , Dyspepsia/drug therapy , Gastric Mucosa/pathology , Humans , Kidney Failure, Chronic/complications , Male , Stomach Diseases/chemically inducedABSTRACT
INTRODUCTION: Standard neurophysiological techniques evaluate thick myelinated fibers. Yet, peripheral nerves are equally composed of thin myelinated and unmyelinated fibers. The latter are responsible for autonomic function as well as temperature and pain perception. DEVELOPMENT: Microneurographic studies are restricted to investigation laboratories. Since the techniques are complex and invasive, their performance is still poor for clinical purposes and some of the components to be analyzed, such as cardiovagal, cannot be directly recorded. The clinical need to evaluate the functions regulated by the autonomic nervous system (ANS) had led to devising a series of tests which, in most cases, rely on reflex responses evoked by already known standardize stimuli. The battery chosen has to be non invasive, reproducible, specific, providing relevant data to the investigated function, with a readily available technology, which has to be managed being aware of the physiological and pathological factors that might bear an influence on the results. The recent development of heart rate and blood pressure power spectral analysis, provides a new interesting insight for quantification of ANS abnormalities. The study of thermography and thermometry of body surface brings forward evidence on the activity of other thin and unmyelinated fibers components of the peripheral nerve spectrum. CONCLUSION: The adequate management of the above mentioned tests gives rise to a more extensive and appropriate knowledge of the whole peripheral nerve fiber spectrum.
Subject(s)
Myelin Sheath/physiology , Nerve Fibers, Myelinated/physiology , Arrhythmias, Cardiac/diagnosis , Autonomic Nervous System/physiology , Blood Pressure/physiology , Heart Rate/physiology , Humans , Pain/physiopathology , Peripheral Nerves/physiology , Sweat Glands/physiologyABSTRACT
INTRODUCTION: Disfunction of thin myelinated and unmyelinated fibers may appear isolated or in association with large-myelinated fibers lesion. Small-fiber neuropathy includes autonomic and sensory symptoms, most prominent of them thermo-algesic deficits. DEVELOPMENT AND CONCLUSION: In some acute neuropathies, small-fiber lesion is relatively pure, as in pandysautonomia, but it also appears in disorders with prominent somatic involvement, such as the Guillain-Barre syndrome, in which case autonomic symptoms worsens the prognosis. Small-fiber dysfunction is important in certain diseases that involve different components of the nervous system, like paraneoplastic syndromes and porphyria. Some drugs and toxic substances may damage thin myelinated and unmyelinated fibers. Nowadays, chronic idiopathic small-fiber neuropathy is diagnosed more frequently, because of the recent development of techniques that selectively evaluate this peripheral nerve component. Hereditary sensory and autonomic neuropathies can also be studied. Small-fiber dysfunction is very prominent in some diseases, e.g. diabetes mellitus and amyloidosis. In the pure autonomic failure, only the peripheral component of the autonomic nervous system is affected, and this feature is the key to make diagnosis versus multisystem atrophy. There are situations in which there is no clear deviation from normality, namely old age autonomic failure and orthostatic intolerance syndrome in which autonomic evaluation is mandatory.
Subject(s)
Nerve Fibers, Myelinated/pathology , Peripheral Nervous System Diseases/pathology , Acute Disease , Adie Syndrome/complications , Amyloidosis/complications , Botulism/complications , Diabetes Complications , Guillain-Barre Syndrome/complications , HIV Infections/complications , Humans , Paraneoplastic Syndromes, Nervous System/complications , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/diagnosis , Porphyrias/complicationsABSTRACT
HYPOTHESIS: IL-10 will reduce morbidity and mortality in murine MODS. Introduction. Intraperitoneal (ip) zymosan causes a triphasic inflammatory process leading to MODS. Phase I is an acute systemic inflammatory response to sterile peritonitis. Phase II is the recovery phase. Phase III is characterized by recurrent illness, progressive organ dysfunction, and elevated proinflammatory cytokines. METHODS: Male ICR mice were randomized (on Experiment Day 0, time = 0 h) into four initial groups (A-D): Control Group A received no zymosan and no IL-10. Group B received zymosan (1 mg/g mouse BW, t = 0) and no IL-10. Group C received no zymosan and IL-10 at t = 2 h. Group D received zymosan and IL-10 at t = 2 h. On Experiment Day 4, mice in Groups B-D were randomized into six further treatment groups (B1 and B2, C1 and C2, D1 and D2). Group B1 received no treatment. Group B2 received IL-10 when clinical signs of recurrent illness developed (Phase III, 12-18 days after zymosan treatment). Mice were sacrificed when they were preterminal (clinical signs of shaking, shivering, or paralysis) or on Experiment Day 28 (survivors). Plasma total bilirubin and creatinine levels were measures of organ function. Terminal pulmonary compliance was measured in situ through a physiologic range of tidal volumes. RESULTS: Mice entering Phase III consistently progressed to MODS characterized by elevated bilirubin and hemorrhagic lungs which, if left untreated, was lethal. Mice treated with IL-10 (Group B2) when they entered Phase III had lower mortality (28.6% vs 100%, P < 0.02), longer survival (25 vs 18 days, P < 0.05), and improved lung pulmonary compliance (slope beta1 = 0.082 ml/mm Hg vs 0.059 ml/mm Hg, P < 0.001) compared to untreated (Group B1) mice in Phase III. CONCLUSIONS: IL-10 improves survival even when given after clinical signs of illness are present.
Subject(s)
Interleukin-10/pharmacology , Multiple Organ Failure/drug therapy , Multiple Organ Failure/mortality , Animals , Disease Models, Animal , Disease Progression , Male , Mice , Mice, Inbred ICR , Multiple Organ Failure/chemically induced , Specific Pathogen-Free Organisms , Survival Analysis , ZymosanABSTRACT
INTRODUCTION: Orthostatic hypotension (OH) symptoms are the most frequent reason for patients to undergo an autonomic examination. The incidence of these symptoms is greater in two groups: young people with neurally mediated syncope, and adults older than 60 years, all who have normal results in the EKG and EEG test. The baroreflex afferents induce a continuous blood pressure adjustment through the heart rate variation. There are functional changes with aging which reduce this baroreflex sensitivity and therefore the accommodation to the haemodynamic requirements is frequently impaired. A number of no neurogenic triggers can be implicated in the development of OH symptoms such as electrolytic disorders, arrhythmia with low stroke volume and drugs side effects. MATERIAL AND METHODS: To study the influence of these factors in the elderly suffering from OH, we reviewed patients older than 60 years sent to our laboratory during the last three years. In 40 out of 207 cases we found the existence of some of the above mentioned factors as possible trigger of the symptoms, since no autonomic abnormality was present. After arrhythmia correction, in two cases, and the pharmacologic agent suppression, in four more patients, symptoms disappeared and no OH was found in a second tilting test. OH is a frequent problem in the elderly and requires a careful review of the numerous causes that could contribute to develop the symptoms. CONCLUSIONS: To take the proper therapeutic decision, a long term monitoring seems to be necessary for the main parameters: blood pressure and EKG.
Subject(s)
Baroreflex/physiology , Hypotension, Orthostatic/etiology , Aged , Aging/physiology , Antidepressive Agents/adverse effects , Antidepressive Agents/pharmacology , Arrhythmias, Cardiac/complications , Diuretics/adverse effects , Drug Synergism , Female , Humans , Hypertension/complications , Hypotension, Orthostatic/chemically induced , Hypotension, Orthostatic/physiopathology , Middle Aged , Reflex, Abnormal , Retrospective Studies , Tilt-Table Test , Vasodilator Agents/adverse effects , Vasodilator Agents/pharmacologyABSTRACT
OBJECTIVE: To relate clinical features to autonomic laboratory indices used in the diagnosis of Complex Regional Pain Syndrome type I (CRPS I) (reflex sympathetic dystrophy) to generate improved diagnostic criteria. DESCRIPTION: CRPS I is a chronic pain syndrome, characterized by diffuse limb pain with allodynia and prominent vasomotor and sudomotor dysfunction. METHODS: We conducted a prospective study on 102 patients referred for possible CRPS I. These patients completed a structured questionnaire and underwent neurologic examination, with special attention to the evaluation of clinical features of vasomotor, sudomotor, motor, and sensory, including pain, dysfunction. All patients were tested using a standard autonomic protocol that compared side-to-side skin temperature, resting sweat output, and quantitative sudomotor axon reflex test (QSART) measurements. Composite autonomic clinical (CRPS-Sx) and laboratory (CRPS-LAB) scores were defined. The clinical (subjective and objective) and the laboratory data were analyzed using Pearson's correlation analysis and Bonferroni's probability value to assess concordance and their value in correctly diagnosing CRPS I. RESULTS: All cases occurred after limb injury. One-third of cases did not fulfill our criteria of CRPS I. Highly significant correlations (p<.001) were found among certain clusters of symptoms and signs that shared unifying pathophysiologies. CRPS-Sx correlated with CRPS-LAB (p = .035). The indices that correlated most reliably with clinical data and with each other were RSO, QSART, and skin temperature reductions. CONCLUSION: Clinical and autonomic laboratory probability scores correlate in an internally consistent manner. Both CRPS-Sx and CRPS-LAB are sensitive and reliable tools to formulate a correct diagnosis of CRPS I and can be combined to provide an improved set of diagnostic criteria for CRPS I.