RESUMEN
PURPOSE OF THE STUDY: This manuscript aims to present the method of arthroscopic assisted subtalar arthrodesis and to evaluate the benefi ts of this surgery on our study population. MATERIAL AND METHODS: In the period from 9/2007 to 1/2020, a total of 33 subtalar arthrodesis were performed in 31 patients aged 19-66 years (mean 48 years, median 50 years). The indication for arthrodesis was subtalar arthritis causing pain and gait disorders, or hindfoot deformities (most commonly after a calcaneus bone fracture). The arthroscopic assisted subtalar arthrodesis was performed with autologous tricortical bone block graft harvesting from the pelvis, supplemented by autologous cancellous bone graft. Stabilization was achieved by cannulated screws inserted in neutral ankle position. Patients in our retrospective study were followed up for a mean of 48 months (range, 24-130 months). The patients were evaluated preoperatively and at 2 years after surgery. The hindfoot angles and height (TCA - talocalcaneal angle, CIA - calcaneal inclination angle, TCH - talocalcaneal height) were evaluated on radiographs, bone union was assessed on radiographs and CT scans. The clinical assessment was performed using the ankle-hindfoot scale (AHS) of AOFAS (AOFAS score). RESULTS: The preoperative AOFAS score was 35-68 points (mean 52, median 54), the postoperative AOFAS score at 2 years after arthrodesis was 58-94 points (mean 82, median 82). Both the mean and median values of AOFAS score showed a signifi - cant progress from the poor result to the good and excellent result. After 2 years the TCA value decreased in 18 patients (56%) by no more than 3°. The CIA decrease observed in 21 patients (64%) was by 1° on average. The TCH decrease of 1-5 mm after 2 years since the surgery was seen in 16 patients. In 2 patients incomplete healing of arthrodesis was observed, manifested as a clinically asymptomatic non-union. No deep infection was reported. DISCUSSION: In agreement with the current literature, the arthroscopic subtalar arthrodesis has been confi rmed to be a safe method for the management of consequences of hindfoot fractures, with minimum complications and leading to accelerated bone fusion. Differences can be found in the approach, position, use of cancellous bone graft and surgical techniques. In recent years, prone position, posterior approaches, use of cancellous bone graft, distraction and fi xation with 2-3 screws divergently inserted into the bone prevail. The degree of healing of the bone fusion is generally an important factor. In our study population, non-healing was recorded in 2 patients, namely in the form of a clinically silent non-union. Neurological or early complications and/or osteosynthesis material failure occurred in up to a maximum of 10% of cases. The conclusive results of minimally invasive arthrodesis based on the AOFAS score have been confi rmed by us as well as by most authors. CONCLUSSIONS: Our study confi rmed that the arthroscopic assisted subtalar arthrodesis is a successful, reliable and safe minimally invasive method, with minimum complications, leading to stable arthrodesis. KEY WORDS: subtalar arthrodesis, subtalar arthroscopy.
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Traumatismos del Tobillo , Calcáneo , Fracturas Óseas , Humanos , Estudios Retrospectivos , Artrodesis , Pie , Calcáneo/cirugía , Extremidad InferiorRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive behavior and poor prognosis. We present the first retrospective analysis mapping its incidence and therapeutic outcomes in patients diagnosed and treated from 2000 to 2017 in the Czech Republic. The cohort comprised 14 patients (10 males, 4 females) with a median age at diagnosis of 39 years (range, 5-68 years). Initially, skin involvement was noted in 10 (71%) patients and bone marrow infiltration was present in 9 (64%). The first complete remission was achieved in 6/14 (43%) patients after acute lymphoblastic leukemia/lymphoma induction therapy and in 3/14 (21%) patients after acute myeloid leukemia regimen. Nine patients underwent allogeneic hematopoietic cell transplantation, with two patients achieving the first complete remission only after allogeneic transplantation. Patients undergoing allogeneic hematopoietic cell transplantation had longer overall survival than those treated without transplantation (the median survival over the period 16.4 vs. 8.1 months). Relapse of the disease was a significant predictor of mortality (p=0.05). Over the study period, patients' survival ranged from 3.3 to 44.2 months, with a median overall survival of 13 months. Our results revealed an effectivity of allogeneic hematopoietic cell transplantation on complete remission achievement in refractory/relapsed disease. The study aimed to present the actual data from the Czech Republic and thus contribute to a global understanding of BPDCN.
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Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Niño , Preescolar , República Checa , Células Dendríticas/patología , Femenino , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: The evaluation of multidisplinary care about HIV positive pregnant women in the Czech Republic. DESIGN: Review. SETTINGS: Gynekologicko-porodnická klinika 1. LF UK a Nemocnice na Bulovce, Praha. METHODS: The vertical transmission of HIV infection from mother to fetus occurs most often during birth, still 1-2% of HIV-positive pregnant women will transfer the virus transplacenta. Due to careful screening for HIV during pregnancy, counselling, combination antiretroviral (cART) therapy, childbirth planning and its performance by C-section there appears a significant decrease of the virus transmission to the fetus, its occurrence is around 2%. If the HIV infection is detected in the context of screening for sexually transmitted infections (STIs), we begin with combined antiretroviral therapy (cART) depending on the level of viremia and CD4 as soon as possible. All HIV-positive pregnancies are tested for possible coinfection with hepatitis C. Since the first application of the antiretroviral treatment, the therapy is applies throughout the duration of the pregnancy. The labours of the HIV- positive women in the Czech Republic are scheduled. The primary choice is a caesarean section during the 38th week of pregnancy. CONCLUSION: From 1996-2014 the HIV positive status at 18 months of child age was confirmed in 4 cases in the Czech Republic. Three children were born to mothers whose HIV status was unknown at the time of the birth. Thanks to strict adherence to the interdisciplinary care, HIV positive woman have a chance to deliver a HIV-negative newborn and the risk of the transmission of the virus is significantly low.
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Fármacos Anti-VIH/uso terapéutico , Cesárea , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Educación del Paciente como Asunto , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Niño , Terapia Combinada , República Checa , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Humanos , Recién Nacido , Tamizaje Masivo , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/prevención & controlRESUMEN
The direct fusion methods for repair of spondylolytic defects of the lumbar spine have recently been replaced by transpedicular screw fixation of the affected segment, in combination with PLIF, TLIF or ALIF procedures. However, in clearly indicated cases, such as a younger patient with no intervertebral disc degeneration and only minimal or no displacement of the vertebra, the direct repair techniques have a great advantage over transpedicular fixation because they preserve segmental motion The paper reports on a patient with spondylolysis at L3 who underwent surgery combining the Tokuhashi and Matsuzaki and the Gillet and Petit techniques, which involved a system of transpedicular screws, rods and sublaminar hooks supplemented with a cross-connector to support the base of the spinous process. After surgery, the patient reported pain relief and return to normal activities and CT examination showed bony union of both spondylolytic defects.
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Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Espondilólisis/cirugía , Humanos , Masculino , Adulto JovenRESUMEN
The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.
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Antidepresivos de Segunda Generación/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Morfolinas/uso terapéutico , Antagonistas del Receptor de Neuroquinina-1 , Sustancia P/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Antidepresivos de Segunda Generación/efectos adversos , Antidepresivos de Segunda Generación/metabolismo , Antidepresivos de Segunda Generación/farmacología , Aprepitant , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Trastorno Depresivo/etiología , Trastorno Depresivo/metabolismo , Femenino , Gerbillinae , Cobayas , Humanos , Masculino , Persona de Mediana Edad , Morfolinas/efectos adversos , Morfolinas/metabolismo , Morfolinas/farmacología , Norepinefrina/fisiología , Paroxetina/uso terapéutico , Receptores de Neuroquinina-1/metabolismo , Serotonina/fisiología , Estrés Psicológico/tratamiento farmacológico , Sustancia P/metabolismo , Vocalización Animal/efectos de los fármacosRESUMEN
PURPOSE OF THE STUDY To evaluate retrospectively a group of patients with hyperextension injury to the cervical spine who were treated at the Department of Spinal Surgery of the University Hospital in Motol, Prague, between 2003 and 2006. MATERIAL The group comprised 22 patients, 17 men (77 %) and five women (23 %) in the age range of 35 to 81 years, with an average of 59.5 years. All patients had, in association with the injury, neurological deficit of varying degree. METHODS All patients underwent X-ray and magnetic resonance imaging examination and received methylprednisolone according to the National Acute Spinal Cord Injury Study (NASCIS) 2 trial. Eleven patients had urgent surgery within 24 hours of injury; eight patients were operated on within an interval of 3 days to 2 months because of the seriousness of their state and multiple morbidity; and three patients were treated conservatively. Neurological deficit in terms of upper- and lower-limb mobility was evaluated by the American Spinal Injury Association (ASIA) motor score. The values obtained for the urgently operated patients and for those operated on after a time interval were compared by Wilcoxons two-sample test. The other aspects evaluated included trauma aetiology, level of spinal cord injury, manner of treatment, and intra-operative and post-operative complications. RESULTS The most frequent cause of injury was a low-height fall (13 patients; 59 %); car accidents ranked second (9 patients; 41 %). In five patients (22.7 %) ebriety was found. Eighteen patients had no skeletal injury (81.8 %). Four patients (18.2 %). Four patients (18.2 %) suffered fractures of articular or spinous processes, but the anterior column skeleton was intact in all. The segment most frequently affected by myopathy was C3-C4, then C4-C5 and C5-C6. Decompression was carried out to the extent of myopathy; and in the adjacent segments only if significant stenosis was present. In both subgroups of surgically treated patients (urgent and delayed management), comparisons of the ASIA scores at the time of injury and at one-year follow-up showed no significat improvement in post-operative mobility, as evaluated by Wilcoxons two-sample test at a level of significance a = 5 %. No intra-operative or post-operative complications, except for early death, were recorded. In all patients the wound healed by first intention and no loosening of instrumentation was foud on follow-ups at the out-patient departments. DISCUSSION Although the greatest narrowing of the spinal canal due to spondylosis occurs at the C5-C6 segment, the C4-C5 segment sustained most injuries. Although some relevant papers report no significant difference in improved neurological deficit between patients treated surgically and those undergoing conservative therapy, we prefer surgical management, in most of the cases from the anterior approach, which allows us to remove dorsal osteophytes and perform careful decompression to prevent damage to nerve structures and to preserve those which are still intact. There was no significant difference in the outcome between urgent and delayed trauma management, which is unusual amongst other injuries associated with neurological lesions and this indicates that the timing of surgery must be strictly individual and should be carried out at a time when operative benefit outweighs operative burden. The surgical treatment used should, in the first place, lead to early recuperation and rehabilitation. CONCLUSIONS Hyperextension injuries of the cervical spine are usually associated with serious neurological deficit. A correct algorithm of examination will result in good treatment outcomes. However, these injuries require a therapy that is long-lasting and difficult, with a need for cooperation of anaesthesiologists, spinal surgeons, physical therapists and, last but not least, psychologists. Key words: cervical spine, hyperextension injury, spondylosis, myelopathy.
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Vértebras Cervicales/lesiones , Espondilosis/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Espondilosis/diagnóstico por imagen , Espondilosis/cirugíaRESUMEN
BACKGROUND: The histopathological structure of malignant tumours involves two essential compartments - the tumour parenchyma with the actual transformed cells, and the supportive tumour stroma. The latter consists of specialized mesenchymal cells, such as fibroblasts, macrophages, lymphocytes and vascular cells, as well as of their secreted products, including components of the extracellular matrix, matrix modifying enzymes and numerous regulatory growth factors and cytokines. In consequence, the tumour stroma has the ability to influence virtually all aspects of tumour development and progression, including therapeutic response. AIM: In this article we review the current knowledge of tumor stroma interactions in urothelial carcinoma and present various experimental systems that are currently in use to unravel the biological basis of these heterotypic cell interactions. RESULTS: For urothelial carcinoma, an extensive tumour stroma is quite typical and markers of activated fibroblasts correlate significantly with clinical parameters of advanced disease. Another clinically important variable is provided by the stromal expression of syndecan-1. CONCLUSION: Integration of markers of activated stroma into clinical risk evaluation could aid to better stratification of urothelial bladder carcinoma patients. Elucidation of biological mechanisms underlying tumour-stroma interactions could provide new therapeutical targets.
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Proteínas de Neoplasias/metabolismo , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Urotelio/metabolismo , Urotelio/patología , Animales , Comunicación Celular , Humanos , Modelos BiológicosRESUMEN
OBJECTIVE: To determine the pharmacokinetics, pharmacodynamics and safety of the acetylcholinesterase inhibitor zifrosilone in healthy male volunteers. METHODS: Pharmacokinetics, pharmacodynamics, and tolerance of zifrosilone were studied in a double-blind, sequential, single-escalating-dose, randomized panel design. Each panel consisted of six subjects, with four subjects receiving zifrosilone (10, 30, 60, 90, 120, 150, 200, 250, and 300 mg orally) and two subjects receiving matching placebo. Serial blood samples were obtained for zifrosilone plasma concentrations and red blood cell acetylcholinesterase and butyrylcholinesterase activities. Participating subjects (n = 54) were men between the ages of 18 and 45 years. Each subject had a normal physical examination, electrocardiogram, serum chemistries, hematology, urinalysis, and test for human immunodeficiency virus at screening. RESULTS: A greater than proportionate increase in mean plasma concentration values for area under the curve from time zero to infinity was observed over the 200 to 300 mg dose range groups. Red blood cell acetylcholinesterase showed a dose-inhibition relationship, with a mean maximum inhibition of 20.9% at 10 mg that increased to 62.1% at 300 mg. Butyrylcholinesterase activity was relatively unaffected by zifrosilone (< 20% inhibition at 300 mg). For doses > or = 200 mg, an Emax pharmacodynamic model was used to describe the relationship between zifrosilone plasma concentration and red blood cell acetylcholinesterase inhibition (Emax = 83.8%; EC50 = 0.65 ng/ml). CONCLUSIONS: Zifrosilone showed dose-dependent pharmacokinetics after oral administration and was effective in causing selective inhibition of red blood cell acetylcholinesterase.
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Acetofenonas/farmacología , Acetofenonas/farmacocinética , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/farmacocinética , Compuestos de Trimetilsililo/farmacología , Compuestos de Trimetilsililo/farmacocinética , Acetofenonas/efectos adversos , Administración Oral , Adolescente , Adulto , Inhibidores de la Colinesterasa/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Eritrocitos/enzimología , Humanos , Masculino , Compuestos de Trimetilsililo/efectos adversosRESUMEN
Carbamazepine alone or carbamazepine plus neuroleptic was administered to 20 chronic schizophrenic patients. Upon abrupt discontinuation two of the 20 patients had exacerbations of their psychoses characterized by paranoia, hostility, and agitation. The authors discuss the possibility of a carbamazepine withdrawal syndrome.
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Carbamazepina/efectos adversos , Esquizofrenia/tratamiento farmacológico , Psicología del Esquizofrénico , Síndrome de Abstinencia a Sustancias/etiología , Adulto , Antipsicóticos/uso terapéutico , Carbamazepina/uso terapéutico , Enfermedad Crónica , Quimioterapia Combinada , Hospitalización , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Retrospective chart review of 30 Asian patients and 30 matched Caucasian patients failed to replicate a previous report's finding that Asian patients require lower doses of neuroleptic medications than do Caucasian patients.
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Antipsicóticos/administración & dosificación , Pueblo Asiatico , Trastornos Psicóticos/tratamiento farmacológico , Adulto , Clorpromazina/administración & dosificación , Femenino , Hospitalización , Humanos , Masculino , Trastornos Psicóticos/psicología , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológicoRESUMEN
Carbamazepine was given to 12 chronic, treatment-refractory schizophrenic patients for 5 weeks. No overall change was found, but four patients significantly improved while eight worsened. Given the paucity of successful treatments for refractory schizophrenia, further study of carbamazepine appears warranted.
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Carbamazepina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Ensayos Clínicos como Asunto , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico , Psicología del EsquizofrénicoRESUMEN
The authors implemented a new procedure for analyzing phencyclidine (PCP) content in hair. They compare the results of analyses of hair with results of analyses of blood and urine in 47 patients newly hospitalized with acute psychiatric illness. Hair analysis identified 11 patients who had used PCP, and blood and urine analyses did not identify any among the sample population. In three patients, the results of hair analysis aided in establishing a diagnosis of PCP intoxication. The authors discuss interpretations of their findings and psychiatric applications of this new technique.
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Cabello/análisis , Hospitalización , Trastornos Mentales/complicaciones , Abuso de Fenciclidina/diagnóstico , Fenciclidina/análisis , Adulto , Femenino , Humanos , Masculino , Fenciclidina/metabolismo , Fenciclidina/envenenamiento , Abuso de Fenciclidina/complicaciones , Abuso de Fenciclidina/metabolismo , Radioinmunoensayo/métodosRESUMEN
Body temperature is a regulatory function of the hypothalamus. Recently, DeMet et al. (Society for Neuroscience Abstracts Vol 12, 1986) reported that apomorphine stimulation of dopamine autoreceptors caused a significant decrease in metabolic rate in the posterior heat-conserving area of the hypothalamus. The logical hypothesis to follow is that apomorphine administration should induce a decrement in body temperature; this in fact was demonstrated by Cutler et al. (Commun Psychopharmacol 3:375-382, 1979) in humans. It is well known that neuroleptics also disrupt thermoregulation (Clark: Neurosci Biobehav Rev 3:179-231, 1979) and affect dopamine autoreceptors. Therefore, eight chronic treatment-resistant schizophrenics underwent a 6-week single-blind trial of haloperidol and then a subsequent 6-week double-blind trial of clozapine. Both haloperidol and clozapine significantly lowered oral body temperatures relative to baseline washout temperatures. More interestingly, clozapine relative to haloperidol was found to induce a greater decrement in body temperature and was associated with greater clinical improvement. Possible confounding variables are discussed, as is the possible neurochemical basis for the amelioration of psychosis associated with hypothermia.
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Clozapina/uso terapéutico , Dibenzazepinas/uso terapéutico , Haloperidol/uso terapéutico , Hipotermia/inducido químicamente , Esquizofrenia/tratamiento farmacológico , Adulto , Análisis de Varianza , Temperatura Corporal/efectos de los fármacos , Humanos , Masculino , Esquizofrenia/fisiopatologíaRESUMEN
To investigate the pharmacokinetic profile, bioavailability, and dose proportionality of the D2-agonist MK-458 (hydroxypropylmethylcellulose tablet, a sustained release formulation), a 4-period crossover study was conducted in 10 patients with mild to moderate Parkinson's disease (mean age = 63 y; 1 woman, 9 men). Following a titration phase to induce tolerance, each patient was given single oral doses of 6, 12 and 18 mg and a single intravenous 40 micrograms dose (5 micrograms/h over 8h). The maximum concentrations of MK-458 observed in plasma after oral administration were 139, 240 and 344 ng/L for the 6, 12 and 18 mg doses, respectively, and occurred after 8.0, 9.0 and 5.5 h, respectively. Mean areas under the plasma concentration-time curves were 1728, 2849 and 5484 ng/L.h, respectively. The mean plasma half-life was 3.8 h and mean plasma clearance was 3390 ml/min (203.4 L/h). The bioavailability (approximately 5%) was very similar for the 3 tablet formulations tested. The disposition of MK-458 was independent of the dose over the range of doses studied.
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Antiparkinsonianos/farmacocinética , Dopaminérgicos/farmacocinética , Lactosa/análogos & derivados , Metilcelulosa/análogos & derivados , Enfermedad de Parkinson/metabolismo , Administración Oral , Anciano , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/sangre , Preparaciones de Acción Retardada , Dopaminérgicos/efectos adversos , Dopaminérgicos/sangre , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactosa/efectos adversos , Lactosa/sangre , Lactosa/farmacocinética , Masculino , Metilcelulosa/efectos adversos , Metilcelulosa/sangre , Metilcelulosa/farmacocinética , Persona de Mediana Edad , Oxazinas , Enfermedad de Parkinson/sangre , ComprimidosRESUMEN
This double-blind, placebo-controlled, parallel-group, multicenter study was designed to evaluate the safety and efficacy of a new controlled-onset, extended-release formulation of verapamil hydrochloride called physiologic pattern release (PPR) verapamil. The study was conducted at 24 sites (13 United States, 5 Canada, 6 overseas; see Appendix). Following a 1- to 3-week single-blind placebo lead-in period, 278 patients with chronic stable angina pectoris (247 males, 31 females, mean age 60.8 years, range 32 to 78) were randomly assigned to 1 of 4 once-daily, fixed-dose treatment groups: verapamil 180, 360, or 540 mg, or placebo. PPR verapamil at all doses significantly increased (p < 0.05) time to moderate angina and symptom-limited exercise duration, and verapamil 360 mg significantly increased (p < 0.05) time to > or = 1 mm ST-segment depression, after 4 weeks of treatment when assessed 24 hour after the previous dose. Larger doses of verapamil were associated with proportionately greater improvements in exercise tolerance. Frequency of anginal attacks was also reduced by verapamil. The most frequently observed adverse events were dizziness, headache, constipation, and nausea. The incidence of constipation was high (20.9%) within the 540 mg treatment group. This verapamil formulation can be clinically titrated within a 180 to 540 mg dosing range, permitting effective once-daily administration for the treatment of chronic stable angina.
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Angina de Pecho/tratamiento farmacológico , Verapamilo/administración & dosificación , Adulto , Anciano , Análisis de Varianza , Enfermedad Crónica , Estreñimiento/inducido químicamente , Preparaciones de Acción Retardada , Mareo/inducido químicamente , Prueba de Esfuerzo , Femenino , Cefalea/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Método Simple Ciego , Verapamilo/efectos adversos , Verapamilo/uso terapéuticoRESUMEN
Tardive dyskinesia is now widely recognised as a neurological side effect produced in susceptible individuals by ingestion of neuroleptics. In general, the disorder tends to be late in onset, but has also been reported in a small number of individuals who have received neuroleptics for only brief periods. Much effort has been spent searching for predisposing factors, but the only consistent findings are that subjects are usually elderly (and elderly females in particular), in addition to having been exposed to neuroleptic agents. More recently, the increased finding of the presence of buccolingual facial movements in elderly populations never exposed to neuroleptics may bring out a re-evaluation of the role of these agents in the aetiology of tardive dyskinesia. Although much information on tardive dyskinesia has accrued in recent years, the precise definition, subtypes and pathophysiology remain unclear. With the development and availability of standardised rating scales, the clinical description of tardive dyskinesia has expanded from the initial buccolingual masticatory syndrome to include various abnormal movements of the fingers, arms, legs etc. Efforts have been made to distinguish withdrawal tardive dyskinesia from persistent tardive dyskinesia, but, irrespective of the classification, the disorder is in many instances reversible. However, it is impossible at present to predict the reversibility of each patient: therefore early detection of tardive dyskinesia remains an important clinical goal. Pharmacological treatments are based on the currently accepted hypothesis of dopamine receptor hypersensitivity. Selective dopamine blockers (D2) which suppress tardive dyskinesia without causing an increase in Parkinsonian symptoms are at various stages of development. Acetylcholine and gamma-aminobutyric acid (GABA) also appear to play a reciprocal role with dopamine as seen by moderate success using cholinergics and 'GABAergics'. However, there is no completely satisfactory treatment at present, indicating that prevention must be the primary aim. Above all, clinicians should carefully evaluate the indication for neuroleptic drugs, and avoid their use in conditions which may be treated with more benign drugs. A strategy for management of tardive dyskinesia is presented, and indications for withdrawing or continuing neuroleptics, the treatment of withdrawal dyskinesias and the role of experimental therapies are discussed.
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Discinesia Inducida por Medicamentos/terapia , Diagnóstico Diferencial , Discinesia Inducida por Medicamentos/diagnóstico , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/epidemiología , Discinesia Inducida por Medicamentos/fisiopatología , Discinesia Inducida por Medicamentos/prevención & control , Femenino , Humanos , MasculinoRESUMEN
Researchers have sought to understand the underlying pathophysiology of Alzheimer's disease (AD) ever since Dr A Alzheimer first described the condition in 1907. Unfortunately however, until recently, they have done so with limited success. This lack of clarity has deterred advancements in therapeutic drug research beyond all but the purely symptomatic treatment relief currently available. However, through spatio-temporal analysis of the two types of cerebral lesions that characterise the disorder (senile plaques and neurofibrillary tangles) and the compilation of genetic data concerning familial AD, there now exists the foundation for a more comprehensive understanding of the disease. Although symptomatic cholinergic strategies have beneficial effects, their benefits are modest and current research has turned to the development of other promising strategies, including oestrogen replacement, anti-inflammatory agents, free radical scavengers, anti-oxidants and monoamine oxidase-B (MAO-B) inhibitors. Many of these strategies may have some merit, however further analysis and structured research are necessary before a definitive decision can be made about their efficacy and possible role in AD therapy. Strategies that are directed at halting the underlying biochemical changes in AD are nearing clinical testing and offer the promise for meaningful therapeutic outcomes.
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Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/uso terapéutico , Terapia de Reemplazo de Estrógeno , Depuradores de Radicales Libres/uso terapéutico , Inhibidores de la Monoaminooxidasa/uso terapéutico , Enfermedad de Alzheimer/epidemiología , Animales , Inhibidores de la Colinesterasa/uso terapéutico , Ensayos Clínicos como Asunto , Femenino , Humanos , Factores de RiesgoRESUMEN
Mild cognitive impairment (MCI) is a term used to describe memory decline or other specific cognitive impairment in individuals who do not have dementia or significant impairment of other cognitive functions beyond that expected for their age or education. It has been suggested that as much as 38% of the elderly population would meet criteria for MCI and although the associated memory deficits are mild, the fact that up to 15% of MCI patients, particularly those with a particular type of memory impairment, convert to Alzheimer's disease (AD) annually has prompted serious attention. Despite the high conversion rate, MCI cannot be used synonymously with early or mild AD, as patients with AD are impaired not only in memory performance but in other cognitive domains as well; they meet diagnostic criteria for dementia. However, since there is a high conversion rate from MCI to AD, it is likely many with MCI have the underlying neuropathology of AD, though they do not yet meet clinical diagnostic criteria. Therefore, treatment strategies developed for AD, specifically acetylcholinesterase inhibitors and Cox-2 inhibitors, have been among the first employed to treat MCI. It is hoped that by impeding the progression of MCI in this manner, fewer patients will convert to AD. This article will give a brief overview of the condition of mild cognitive impairment and an account of trial methodology and current treatment strategies being employed for MCI.
Asunto(s)
Trastornos del Conocimiento/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéutico , Ensayos Clínicos como Asunto , Depuradores de Radicales Libres/uso terapéutico , Humanos , Proyectos de InvestigaciónRESUMEN
Galanthamine (or galantamine, Reminyl) is a tertiary alkaloid acetylcholinesterase inhibitor (AChEI) which has been approved in several countries for the symptomatic treatment of senile dementia of the Alzheimer's type. Derived from bulbs of the common snowdrop and several Amaryllidaceae plants, (-)-galanthamine (GAL) has long been used in anaesthetics to reverse neuromuscular paralysis induced by turbocurarine-like muscle relaxants and more recently, has been shown to attenuate drug- and lesion-induced cognitive deficits in animal models of learning and memory. GAL directly inhibits acetylcholinesterase activity, while demonstrating much weaker activity on butyrylcholinesterase (BuChE). GAL also stimulates pre- and postsynaptic nicotinic receptors, although the clinical significance of this finding is yet unclear. Numerous variants and analogues of GAL have also been developed, with varying potency in inhibiting AChE activity. GAL is readily absorbed after oral administration, with a t(max) of 52 min and a plasma elimination t(1/2) of 5.7 h. The efficacy of GAL administered to Alzheimer's disease (AD) patients has been well demonstrated by large-scale clinical trials. Typical of AChEIs, the most common adverse events associated with GAL are nausea and vomiting. In conclusion, evidence to date suggests galanthamine to be similar to other AChEIs in improving cognitive function in AD patients.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Galantamina/uso terapéutico , Enfermedad de Alzheimer/psicología , Animales , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Galantamina/química , Galantamina/farmacología , HumanosRESUMEN
Rabbit type-specific opsonic antibodies to type 1 and type 12 streptococci were isolated by affinity chromatography on immobilized phage-enzyme extract. They were tested by precipitation in gel, bactericidal test and radioimmunoassay. Only type-specific activities were demonstrated. These activities were distributed homogeneously according to avidity. No suggestion of opsonizing and precipitating activities being separable from each other was found. These highly purified rabbit antibodies were marked by radioiodination and used to titrate human anti-M antibodies by competition. These marked antibodies were also used for the study of type-specific antigenic determinants on streptococcal antigens.