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BACKGROUND: Subtalar arthrodesis through an open approach carries significant risk of complications. An arthroscopic approach aims to minimise damage to the soft tissue envelope to improve recovery, union and complication rates. A two portal approach through the sinus tarsi was used. METHODS: A retrospective review of all patients undergoing isolated arthroscopic arthrodesis was performed. RESULTS: Seventy-seven procedures were performed. Successful arthrodesis was achieved in 75 (97.4%). Two patients underwent successful revision arthrodesis for aseptic nonunion. There was one (1.3%) superficial infection and one (1.3%) partial sural nerve injury. CONCLUSIONS: Two-portal sinus tarsi arthroscopic subtalar arthrodesis is safe and effective. Advantages over other arthroscopic approaches are the access to all three facets of the joint, avoidance of a posterolateral portal in order to minimise risk to the sural nerve, and the ability to use the same approach to arthrodese the entire triple hindfoot joint complex. Technical tips and pitfalls are discussed.
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Artrodesis/métodos , Artroscopía/métodos , Artropatías/cirugía , Articulación Talocalcánea/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Artropatías/diagnóstico , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Articulación Talocalcánea/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To review patients that have undergone correction of a symptomatic femoral malunion using osteotomy combined with decortication. METHODS: A retrospective review of all patients who have undergone decortication and multiplanar osteotomy, looking at the pre-operative deformity, correction achieved, time to union and complications. RESULTS: Seven patients underwent correction under the senior author from 2003 to 2012. Average age was 46 years (range 32-60 years). All had femoral shortening deformity (average 2.7 cm, range 2-4 cm). Each also had at least one other plane of deformity with rotation being the next most commonly encountered in 5 out of the 7 (average 33°, range 0°-45°). Two had tri-planar deformity with the five having bi-planar deformity. Average time to union was 16.3 months (range 7-39 months) with an average of 1.5 operations (range 1-3 operations) to union. One patient has a non-union after five corrective operations. CONCLUSION: Correction of multiplanar deformity of the femur is challenging. Osteotomy with decortication provides a technique to achieve significant femoral multiplanar deformity correction in a single operation. This publication provides technical description of the operative technique, guidance and results.
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Alargamiento Óseo/métodos , Fracturas del Fémur/cirugía , Fracturas Mal Unidas/cirugía , Diferencia de Longitud de las Piernas/cirugía , Osteotomía , Adulto , Diáfisis/lesiones , Diáfisis/cirugía , Fracturas del Fémur/complicaciones , Fracturas Mal Unidas/complicaciones , Humanos , Diferencia de Longitud de las Piernas/etiología , Persona de Mediana Edad , Estudios Retrospectivos , Rotación , Resultado del TratamientoRESUMEN
OBJECTIVES: The burden of stroke on healthcare services in sub-Saharan Africa (SSA) is increasing. However, long-term outcomes from stroke in SSA are not well described. We aimed to investigate case-fatality and health outcomes for stroke survivors at 7- to 10-year follow-up. MATERIALS AND METHODS: The Tanzanian Stroke Incidence Project (TSIP) recruited incidence stroke cases between 2003 and 2006. We followed up cases in 2013, recording date of death in those who had died. RESULTS: Of 130 stroke cases included in this study, case-fatality and date of death data were available for 124 at 7-10 years post-stroke. Of these, 102 (82.3%) had died by 7 years post-stroke. Functional disability, as measured by the Barthel index immediately post-stroke, was a significant predictor of case-fatality at seven-year follow-up with those with severe disability having an almost four-fold increase in the odds of death compared with those with no, mild or moderate disability. CONCLUSIONS: Case-fatality rates are higher than reported in high-income countries, with post-stroke disability a significant predictor of death. Sustainable interventions to reduce post-stroke disability in this setting should be investigated.
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Personas con Discapacidad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/epidemiología , Tasa de Supervivencia/tendencias , Tanzanía/epidemiologíaRESUMEN
We conducted a randomised exploratory trial in children aged between one and sixteen years old to establish the time to achieve an end-tidal oxygen fraction ≥ 0.9 in three different positions: supine, and 30 and 45° head up. We recruited 120 children analysed in two age groups: 1-8 years and 9-16 years. The median (IQR [range]) time to reach the end point was 80 (59-114 [41-295]) s in the younger group and 150 (107-211 [44-405]) s in the older group, regardless of position (p = 0.0001). The end point was reached in 90% of children in approximately 160 s in the younger, and 271 s in the older, groups, respectively. There was no statistical difference between the three positions within each age group in the time to reach the endpoint (p = 0.59). Only two patients in the older age group could not reach the end point, due to poorly fitting facemasks. We conclude that pre-oxygenation can therefore be achieved effectively in most children, and that tilting children head up by 30 or 45° does not significantly reduce the time taken to achieve an end-tidal oxygen fraction of ≥ 0.9. The recommended period for pre-oxygenation in both groups should remain at 3 min but it should be noted that this may be insufficient for many older patients.
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Hipoxia/prevención & control , Oxígeno/administración & dosificación , Postura/fisiología , Respiración , Adolescente , Factores de Edad , Niño , Preescolar , Humanos , Lactante , Posición Supina , Factores de TiempoRESUMEN
BACKGROUND: Caregiver burden includes the many physical, mental and socio-economic problems arising from caring for individuals with chronic and disabling diseases. Being a carer in sub-Saharan Africa (SSA), where little is known about chronic neurological conditions, may be extremely demanding. Conversely, multigenerational living may allow sharing of care among many caregivers. We wished to determine the relative burden of caring for two chronic neurodegenerative conditions (Parkinson's disease (PD) and dementia) in rural Tanzania. METHODS: All surviving patients from a PD prevalence study, newly identified people with PD from a neurological disorders study and all people with dementia from a dementia prevalence study in Hai, rural Tanzania, were invited to participate. The Zarit Burden Interview (ZBI) was used to determine level of caregiver strain (higher score reflects more strain). RESULTS: Of 25 PD patients ZBI was recorded in 20 (14 male). Five had no identifiable carer as they were largely independent. Three had PD dementia (PDD). Of 75 people with dementia (excluding 3 PDD), 43 (32 female) completed the ZBI. For the other 32, the caregivers felt the care they provided was a normal intergenerational expectation. Median ages were 78.5 and 85 years for PD and dementia, respectively. Median ZBI was 30.5 for PD and 14 for dementia (U = 166.0, z = -3.913, p < 0.001). Disease duration and disease type (PD or dementia) were univariate predictor of ZBI score, although only disease type was predictive by multivariable linear regression. CONCLUSIONS: Caring for an individual with PD may be more burdensome than caring for an individual with dementia in SSA. People with more advanced PD had higher caregiver burden.
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Cuidadores/psicología , Costo de Enfermedad , Demencia/terapia , Enfermedad de Parkinson/terapia , Calidad de Vida/psicología , Actividades Cotidianas , Adaptación Psicológica , Anciano , Anciano de 80 o más Años , Demencia/diagnóstico , Demencia/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Escalas de Valoración Psiquiátrica , Factores Socioeconómicos , Encuestas y Cuestionarios , TanzaníaRESUMEN
OBJECTIVES: There are few data on neurological disorders prevalence from low- and middle-income countries, particularly sub-Saharan Africa (SSA) and none specific to the African elderly. We aimed to determined the prevalence of neurological disorders in those aged 70 years and over in a rural African community. MATERIALS AND METHODS: This study was a cross-sectional two-phased community epidemiological survey set in the rural Hai district of Tanzania. Screening was performed with a validated screening questionnaire with high sensitivity and specificity. Positive responders to screening underwent full neurological history and examination to confirm or refute the presence of neurological disorders and to classify the disorder using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). RESULTS: Of 2232 participants, there were 384 neurological diagnoses amongst 349 people. The age-adjusted prevalence of people with neurological diagnoses was 154.1 per 1000 (95% CI 139.2-169.1). The age-adjusted prevalence per 1000 of the most common neurological disorders were tremor (48.2), headache (41.8), stroke (23.0), peripheral polyneuropathy (18.6), upper limb mononeuropathy (6.5) and parkinsonism (5.9). CONCLUSIONS: This is the first published community-based neurological disorders prevalence study specifically in the elderly in SSA. It reveals a high prevalence of neurological morbidity and demonstrates the contribution neurological disorders make to the non-communicable disease epidemic. This is likely to increase as the population of low-income countries ages constituting a public health dilemma.
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Enfermedades del Sistema Nervioso/epidemiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Población Rural/estadística & datos numéricos , Tanzanía/epidemiologíaRESUMEN
INTRODUCTION: With the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic. MATERIALS AND METHODS: A protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 'clean' site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff. RESULTS: A total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive. CONCLUSION: This study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.
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Procedimientos Quirúrgicos Electivos/métodos , Neoplasias/cirugía , Procedimientos Quirúrgicos Operativos/métodos , Tiempo de Tratamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Ambulatorios/métodos , Derivación Arteriovenosa Quirúrgica , COVID-19 , Prueba de Ácido Nucleico para COVID-19 , Cateterismo Cardíaco , Atención a la Salud/organización & administración , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Histerectomía , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , SARS-CoV-2 , Reino Unido/epidemiología , Procedimientos Quirúrgicos Urológicos , Adulto JovenRESUMEN
The incidence of Parkinson's disease (PD) in sub-Saharan Africa (SSA) is greater than thought however, is largely undiagnosed and untreated. This study aimed to evaluate a nonpharmacological approach using cueing therapy to improve gait in drug-naïve PD and the feasibility of delivering rehabilitation in northern Tanzania. In this study, twenty-one people with PD aged 76.4 years (12.9 SD) with varying disease severity participated. They received 9 x 30 min sessions of cueing therapy for gait problems over 3 weeks from a trained therapist delivered in their home environment. Cueing therapy consisted of walking in time to a metronome beat to correct step amplitude and step frequency during a range of functional activities. Gait was recorded on video before and after therapy, and videos were analyzed in the UK by an assessor not involved in data collection. Disease severity (UPDRS) and balance were also measured. Patients were assessed in their nearest clinic. Data were analyzed in Minitab and a P value of 0.05 was considered significant. Cueing therapy significantly improved single and dual task walking speed, step amplitude, and single task step frequency. There was also a significant improvement in motor impairment (UPDRS III) and activities of daily living (UPDRS II). The results provide promising evidence for the role of cueing therapy in PD for symptom management to reduce or delay medication onset. This study also supports the feasibility of rehabilitation in PD in community environments in SSA, which may be applicable to other developing regions.
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Estimulación Acústica/métodos , Señales (Psicología) , Trastornos Neurológicos de la Marcha , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/terapia , Anciano , Áreas de Influencia de Salud , Estudios de Factibilidad , Femenino , Trastornos Neurológicos de la Marcha/epidemiología , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/terapia , Humanos , Masculino , Enfermedad de Parkinson/complicaciones , Tanzanía/epidemiologíaRESUMEN
BACKGROUND: Cricoid pressure or to be more exact cricoid force (CF) can cause airway obstruction and subsequent difficulty with airway management during an emergency induction. METHODS: We studied 30 children with an age range of 3 months to 15 yr who presented for routine bronchoscopy or other surgical procedures requiring tracheal intubation. We looked at the effect of CF on the calibre of the subglottic airway and objectively measured the force which caused 50% or greater distortion/compression of the subglottic airway. RESULTS: There was a linear relationship between both age and weight and CF. No patient suffered any adverse effects. Overall, the mean force required to compress the airway was 10.5 N. However, this force could be as low as 5 N in children <1 yr of age, and up to between 15 and 25 N in teenagers. CONCLUSIONS: Forces well below the recommended value of 30 N will cause significant compression/distortion of the airway in a child.
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Obstrucción de las Vías Aéreas/etiología , Cartílago Cricoides/fisiopatología , Reflujo Gastroesofágico/prevención & control , Intubación Intratraqueal/métodos , Presión/efectos adversos , Adolescente , Envejecimiento/fisiología , Obstrucción de las Vías Aéreas/fisiopatología , Peso Corporal/fisiología , Broncoscopía/métodos , Niño , Preescolar , Femenino , Humanos , Lactante , Intubación Intratraqueal/efectos adversos , MasculinoRESUMEN
Enzymes from chick and rat tissues catalyze the reaction of N-methyl tryptamine with 5-methyltetrahydrofolic acid to form 2,3,4,9-tetrahydro-2-methyl-1H-pyrido[3,4b] indole. N,N-Dimethyltryptamine was not formed. With tryptamine as substrate the product is 2,3,4,9-tetrahydro-1H-pyrido[3,4b] indole and not N-methyltryptamine. These pyridoindoles were not formed when S-adenosylmethionine was cosubstrare.
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INTRODUCTION: Estimates of the prevalence of essential tremor (ET) vary widely but there are few existing data on the prevalence of ET in sub-Saharan Africa. PATIENTS AND METHODS: A door-to-door community based prevalence study of ET was carried out in the Hai district of northern Tanzania (n = 161,071). The screening questionnaire was followed by examination of positive responders and backed up with other case finding methods. RESULTS: 222 patients responded positively to the screening questions and 43 were referred by village elders. 65 (38 men, 27 women) were diagnosed with ET. Mean age was 72 years and mean duration of symptoms was 11.3 years. The crude prevalence rate was 41/100,000 and age standardised prevalence compared with the UK population (2001) was 82/100,000. DISCUSSION: This is the first community based prevalence study of ET in sub-Saharan Africa. Previous data from community based neurological surveys showed lower prevalence rates of 5/100,000 in Ethiopia and 10/100,000 in Nigeria. Non-selective beta blockers are available locally and are affordable, yet none of these patients had previously been on any treatment.
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Temblor Esencial/epidemiología , Población Rural/estadística & datos numéricos , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Prevalencia , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Tanzanía/epidemiologíaRESUMEN
BACKGROUND: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults. This study assesses clinical utility of two instruments, the IDEA cognitive screen and the Confusion Assessment Method (CAM) for identification of delirium in older adults admitted to medical wards of a tertiary referral hospital in Tanzania. METHOD: The IDEA cognitive screen and CAM were administered to a consecutive cohort of older individuals on admission to Kilimanjaro Christian Medical Centre using a blinded protocol. Consensus diagnosis for delirium was established against DSM-5 criteria and dementia by DSM-IV criteria. RESULTS: Of 507 admission assessments, 95 (18.7%) had DSM-5 delirium and 95 (18.7%) had DSM-IV dementia (33 (6.5%) delirium superimposed on dementia). The CAM and IDEA cognitive screen had very good diagnostic accuracy for delirium (AUROC curve 0.94 and 0.87 respectively). However, a number of participants (10.5% and 16.4% respectively) were unable to complete these screening assessments due to reduced consciousness, or other causes of reduced verbal response and were excluded from this analysis; many of whom met DSM-5 criteria for delirium. Secondary analysis suggests that selected cognitive and observational items from the CAM and IDEA cognitive screen may be as effective as the full screening tools in identifying delirium even in unresponsive patients. CONCLUSION: Both instruments appeared useful for delirium screening in this inpatient setting, but had significant limitations. The combination of assessment items identified may form the basis of a brief, simple delirium screening tool suitable for use by non-specialist clinicians. Further development work is needed.
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Delirio/diagnóstico , Delirio/epidemiología , Demencia/diagnóstico , Demencia/epidemiología , Evaluación Geriátrica , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Pacientes Internos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Estadísticas no Paramétricas , Tanzanía/epidemiología , Escala Visual AnalógicaRESUMEN
This study evaluated the symptom burden experienced by patients with Idiopathic Parkinson's Disease (IPD) by using a standard palliative care assessment tool (PACA) and comparing it with the Unified Parkinson's Disease Rating Scale (UPDRS). These tools together with the Mini-Mental State Examination, Beck Depression Inventory and the Schedule for the Evaluation of Individual Quality of Life were used in 123 IPD patients. The PACA demonstrated broad coverage of both motor and non motor symptoms (mean=14.3 symptoms per patient) whereas the UPDRS predominantly assessed motor symptoms. Implications for symptom assessment and palliative care provision in IPD are discussed.
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Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Psicometría , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Perfil de Impacto de EnfermedadRESUMEN
The colonization of the gut with microbes in early life is critical to the developing newborn immune system, metabolic function and potentially future health. Maternal microbes are transmitted to offspring during childbirth, representing a key step in the colonization of the infant gut. Studies of infant meconium suggest that bacteria are present in the foetal gut prior to birth, meaning that colonization could occur prenatally. Animal studies have shown that prenatal transmission of microbes to the foetus is possible, and physiological changes observed in pregnant mothers indicate that in utero transfer is likely in humans as well. However, direct evidence of in utero transfer of bacteria in humans is lacking. Understanding the timing and mechanisms involved in the first colonization of the human gut is critical to a comprehensive understanding of the early life gut microbiome. This review will discuss the evidence supporting in utero transmission of microbes from mother to infants. We also review sources of transferred bacteria, physiological mechanisms of transfer and modifiers of maternal microbiomes and their potential role in early life infant health. Well-designed longitudinal birth studies that account for established modifiers of the gut microbiome are challenging, but will be necessary to confirm in utero transfer and further our knowledge of the prenatal microbiome.
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Feto/microbiología , Microbioma Gastrointestinal , Animales , Bacterias , Parto Obstétrico , Femenino , Humanos , Lactante , Recién Nacido , Madres , EmbarazoRESUMEN
The biosynthesis of neutral lipids in Mycobacterium smegmatis was studied using cell free extracts. Maximum neutral lipid production was obtained when the reaction mixture (400 microliter) consisted of 0.25 M potassium phosphate buffer (pH 7.5), 0.125 mM oleoyl-CoA, 3.75 mM sn-glycerol-3-P, 10 mM MgCl2 and 1.85 mg bovine serum albumin. No magnesium dependency for the acylation of sn-glycerol-3-P was observed. A slight stabilizing effect seemed to occur due to this ion. The enzyme phosphatidate phosphohydrolase, on the other hand, was shown to be magnesium dependent. The activity of this enzyme also appeared to be stimulated by high concentration (0.75 to 1.25 mM) of ATP which enhanced lipid formation at all concentrations tested (0.25 to 3.75 mM). A heat-stable protective factor having a molecular weight less than 16 000 which caused a stimulatory effect on sn-glycerol 3-phosphate acyltransferase activity was found in the cell-free extracts. Preliminary experiments suggest that the factor might be polysaccharide in nature.
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Lípidos/biosíntesis , Mycobacterium/metabolismo , Acilcoenzima A/metabolismo , Adenosina Trifosfato/farmacología , Sistema Libre de Células , Citidina Trifosfato/farmacología , Congelación , Glicerol/metabolismo , Concentración de Iones de Hidrógeno , Magnesio/farmacología , Polisacáridos Bacterianos/farmacología , Albúmina Sérica Bovina/farmacología , Triglicéridos/biosíntesisRESUMEN
Previously described methods for identification of proteins separated in cylindrical polyacrylamide gels have been found to be costly in time and antiserum and difficult to apply to small amounts of protein as are found in cerebrospinal fluid. We describe a method which involves printing of the proteins on the cut surface of the gel onto nitrocellulose paper. The protein bands of the imprint can then be identified using labelled antibodies. We have found this to be economical and quick, and it has permitted sensitive and reliable identification of proteins in unconcentrated cerebrospinal fluid and aqueous humour.
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Proteínas Sanguíneas/aislamiento & purificación , Proteínas del Líquido Cefalorraquídeo/aislamiento & purificación , Proteínas/aislamiento & purificación , Electroforesis en Gel de Poliacrilamida/métodos , Humanos , Sueros InmunesRESUMEN
Thirty-three patients were treated with intravenous (IV) cisplatin (CPDD) of whom 32 were considered evaluable. There were 14 medulloblastomas, five primitive neuroectodermal tumors (PNET), nine gliomas, three ependymomas, and one germ cell tumor. The overall response rate was 13 of 32 (41%). Eleven responses (five complete [CR], five partial [PR], one mixed [MR]) were noted in the patients with medulloblastoma. The response rate within this group was 79%. Toxicity was tolerable, although it precluded further therapy in five patients.
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Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Niño , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Glioma/tratamiento farmacológico , Humanos , Masculino , Meduloblastoma/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológicoRESUMEN
A transient acute neurologic syndrome occurred in 22 patients receiving high-dose methotrexate (HDMTX) (8 to 9 g/m2) for a variety of malignancies. The neurologic signs were similar in all cases. The syndrome occurred an average of six days after the second or third weekly treatment. Common findings included behavioral abnormalities, focal sensorimotor signs, and abnormal reflexes. Signs often alternated from one side to the other. Evaluations including computed tomography (CT) scan, lumbar puncture, hemogram, and blood chemistry were normal. The EEG revealed some slowing in all cases. The cause of this syndrome is unknown. It is transient and usually does not recur. Its appearance does not preclude further treatment with HDMTX.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encefalopatías/inducido químicamente , Metotrexato/efectos adversos , Adolescente , Adulto , Conducta/efectos de los fármacos , Encefalopatías/fisiopatología , Electroencefalografía , Femenino , Glioma/tratamiento farmacológico , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Meduloblastoma/tratamiento farmacológico , Metotrexato/administración & dosificación , Metotrexato/líquido cefalorraquídeo , Osteosarcoma/tratamiento farmacológico , Paresia/inducido químicamente , Convulsiones/inducido químicamente , SíndromeRESUMEN
PURPOSE: Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS: Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS: Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION: Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Germinoma/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Carboplatino/administración & dosificación , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Femenino , Germinoma/mortalidad , Germinoma/patología , Humanos , Lactante , Masculino , Tasa de SupervivenciaRESUMEN
Over a 22-month period, we investigated optic and otic toxicity accompanying intra-arterial cisplatin therapy. Baseline and serial neurologic and ophthalmologic examinations, visual evoked potentials, and brain-stem auditory evoked potentials were performed in six patients, aged 37 to 53 years. Patients received infraophthalmic intra-arterial cisplatin (60 mg/m2) every month for three to 10 treatments (mean, six treatments). Five of the six patients had progressive optic toxicity. In two patients, the visual evoked potential prolongation preceded acuity loss by at least 4 months. Two patients had evidence of otic toxicity by either brain-stem auditory evoked potential or click threshold and brain-stem auditory evoked potential. Intra-arterial cisplatin neurotoxicity may be significant in patients with already limited survival. Visual evoked potential and brain-stem auditory evoked potential should be used to monitor patients receiving potentially neurotoxic therapy.