Glycemia in Acute Stroke II study: a call to improve post-stroke hyperglycemia management in clinical practice.

BACKGROUND AND PURPOSE: The aim of the study was to analyze the effect of conventional glucose management, which aimed to maintain glucose levels <155 mg/dL (8.5 mmol/L), on glucose control and the outcomes of patients with acute ischaemic stroke (IS) in a clinical practice setting. METHODS: This was a multicenter, prospective cohort study of patients with acute IS. Patients were classified into four groups based on their initial 48-h capillary glucose levels and the administration of and response to corrective treatment: (i) untreated and maximum glucose levels <155 mg/dL (8.5 mmol/L) within the first 48 h; (ii) treated and good responders [glucose levels persistently <155 mg/dL (8.5 mmol/L)]; (iii) treated and non-responders [any glucose values ≥155 mg/dL (8.5 mmol/L) during the 24 h after the start of corrective treatment]; and (iv) untreated with any glucose value ≥155 mg/dL (8.5 mmol/L). The primary outcome was death or dependence at 3 months (blinded rater). RESULTS: A total of 213 patients were included. Ninety-seven (45.5%) patients developed glucose levels ≥155 mg/dL (8.5 mmol/L), 69 (71.1%) underwent corrective treatment and 31 patients underwent no corrective treatment at the physician's discretion [28 of whom had isolated values ≥155 mg/dL (8.5 mmol/L)]. Only 11 (16%) patients responded to conventional treatment, whereas 58 (84%) patients were non-responsive. Non-responders showed a twofold higher risk of death or dependence at 3 months (odds ratio, 2.472; 95% confidence interval, 1.096-5.576; P = 0.029). CONCLUSIONS: Lack of response to conventional treatment for glucose management in acute IS is frequent and associated with poor outcomes.

Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a retrospective study of 63 patients.

BACKGROUND: Cyclosporine A (CSA) is an immunosuppressant agent widely used in severe atopic dermatitis (AD). However, experience in children is limited. OBJECTIVES: To assess the efficacy and adverse events of CSA therapy in children. METHODS: Retrospective study of children with severe AD treated with CSA between January 2009 and December 2015. RESULTS: Data from 63 patients were collected. Mean age at the beginning of treatment was 8.4 years (±3.6). The median starting dose was 4.27 (±0.61) mg/kg/day. After 4 weeks of treatment, the outcome was excellent in 35% of cases, good in 29% and poor in 36% of the patients. The response was better in patients without eosinophilia (P < 0.05). The median duration of treatment was 4.6 months (range 1.5-21.6). Side-effects were frequent but mild, being more common in patients after longer treatment periods (P < 0.05). Mean time of follow-up was 19.4 months (±12.7). Prolonged remission (>6 months) was observed in 13 patients (20%). LIMITS: This is a retrospective review. The follow-up period is limited. CONCLUSIONS: Our data confirm that CSA is efficacious and acts rapidly in the majority of children with severe AD. CSA therapy can provide sustained remission in some patients. CSA seems to be well tolerated in children, but strict monitoring is mandatory.

Preventing diarrhoea in enteral nutrition: the impact of the delivery set hang time.

BACKGROUND: To meet the current recommendations for enteral tube feeding (ETF), we updated our previous practice in 2011 and began to use a 24-h delivery set hang time (DSHT). We evaluated the impact of this update on the risk of diarrhoea and in diarrhoea-free survival. METHODS: Observational, retrospective study with historical controls on ischaemic and haemorrhagic stroke patients undergoing ETF. Diarrhoea occurrence (≥ 3 liquid stools in 24 h) was compared between patients with a 24 h DSHT (2011-2014) and a 72/96 h DSHT (2010-2011). The analysis was conducted using Kaplan-Meier curves and a Cox regression model. RESULTS: A total of 175 patients were included [median age 81 years (IQR = 12), 46.9% males], 103 in the group with a 24 h DSHT and 72 in the group with a 72/96 h DSHT. The group with a 24 h DSHT had a lower diarrhoea frequency (13.6% vs. 34.7%, risk ratio: 0.39, 95% CI: 0.22-0.70, p = 0.001) and a lower diarrhoea incidence rate (0.87 vs. 2.32 cases of diarrhoea/100 patient*day, rate ratio: 0.37, 95% CI: 0.19-0.72, p = 0.004). The Kaplan-Meier curves showed a longer diarrhoea-free survival for this group (p = 0.003, log-rank test). A 24 h DSHT was associated with a lower risk of diarrhoea (HR = 0.27, 95% CI: 0.12-0.61, p = 0.002), adjusted by albumin, stroke severity, intravenous thrombolysis, the administration of clindamycin and cefotaxime, and the administration of an enteral formula for diabetic patients. CONCLUSIONS: The 24 h DSHT was independently associated with a lower risk of diarrhoea and longer diarrhoea-free survival in hospitalised patients with acute stroke under ETF, compared with a 72/96 h DSHT.

Enteral tube feeding of patients with acute stroke: when does the risk of diarrhoea increase?

BACKGROUND/AIM: We aimed to evaluate the relationship between the length of time acute stroke patients underwent enteral tube feeding (ETF) and episodes of diarrhoea, and to investigate the temporal cut-off point at which diarrhoea risk increases. METHODS: An observational, retrospective study was conducted on patients with acute stroke admitted to a Stroke Centre. Patients undergoing ETF (ETF group) and those not undergoing ETF (control group) were analysed and matched by age and stroke severity. Data regarding demographic and clinical variables were recorded. The analysis was conducted using a receiver operating characteristic (ROC) curve and multivariate analyses. RESULTS: A total of 130 inpatients was included (age 75.08 ± 11.53 years, 56.2% men). The ETF group had higher diarrhoea frequency (27.7% vs 6.2%, P = 0.001). The length of time on ETF was associated with diarrhoea development (odds ratio (OR), 1.12 increment per day; 95% confidence interval (CI) 1.05-1.18; P < 0.001), after adjusting for confounders. The ROC curve showed 7 days on ETF as a cut-off point for diarrhoea risk. Seven days or more on ETF was independently associated with diarrhoea (OR, 6.26; 95% CI 1.66-23.62; P = 0.007), whereas less than 7 days was not when compared with the control group (OR, 0.38; 95% CI 0.04-3.91; P = 0.413). CONCLUSIONS: The length of time on ETF is associated with diarrhoea development in patients with acute stroke, demonstrating a temporal cut-off point. Seven days or longer on ETF is related to the occurrence of diarrhoea, whereas less than 7 days on ETF does not show this effect.

Atrial fibrillation in young stroke patients: do we underestimate its prevalence?

BACKGROUND AND PURPOSE: The prevalence of atrial fibrillation (AF) in young stroke patients has rarely been reported and is considered an uncommon ischaemic stroke (IS) aetiology. Our objective was to analyse the prevalence of AF in IS patients up to 50 years of age and its relationship with stroke severity and outcomes. METHODS: This was an observational study of consecutive IS patients up to 50 years of age admitted to a stroke centre during a 5-year period (2007-2011). A complete cardiology study was performed with a daily electrocardiogram and cardiac monitoring for 72 h as well as echocardiography. In cases of stroke of unknown aetiology a 24-h Holter monitoring was performed. Baseline data, previously or newly diagnosed AF, structural heart disease (SHD) (valvulopathy/cardiomyopathy), stroke severity on admission as measured by the National Institutes of Health Stroke Scale (NIHSS) (moderate-severe stroke if NIHSS ≥ 8) and 3-month outcomes according to the modified Rankin Scale (mRS) (good outcome if mRS ≤ 2) were analysed. AF was classified as AF associated with SHD (AF-SHD) and AF not associated with SHD (AF-NSHD). RESULTS: One hundred and fifty-seven patients were included (mean age 43 years, 58.6% male). Fourteen subjects (8.9%) presented with AF, four with AF-NSHD and 10 with AF-SHD. AF was previously known in 10 patients (6.3%), two with AF-NSHD and eight with AF-SHD. A multivariate analysis showed an independent association between AF and moderate-severe IS (odds ratio 3.771, 95% CI 1.182-12.028), but AF was not an independent prognostic factor. CONCLUSION: AF may be more common than expected in young patients with IS and is associated with increased NIHSS scores.

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome.

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7%, vs 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

Peripheral facial nerve palsy in children during the COVID-19 pandemic. / Parálisis facial periférica en población pediátrica durante la pandemia de la COVID-19.

OBJECTIVES: During the COVID-19 pandemic, an increased frequency of peripheral facial nerve palsy has been described in adults and children. The etiology of the disease during this time remains unclear, since most cases occurred in patients who tested negative for SARS-CoV-2 infection. PATIENTS AND METHODS: Retrospective study of pediatric cases of facial nerve palsy treated during the first year of the pandemic in the emergency department of a children´s hospital located in one of the areas with the highest prevalence of COVID-19 in Spain. Data from this period are compared with cases from the previous three years. RESULTS: Twenty-nine patients with Bell's palsy were included. Over the previous three years combined, 24 patients presented with the same condition, a more than threefold increase. No clinical differences were found between the groups apart from the fact that fewer patients received corticosteroids during the pandemic (13.8% vs 41.6%; p = 0.022). Fourteen children underwent microbiologic testing for active SARS-CoV-2 infection (12 polymerase chain reaction, two rapid antigen test); all were negative. Thirteen patients received serologic testing, two with a positive IgG (15.3%). CONCLUSION: A substantial increase in hospital presentations for facial nerve palsy was observed among children and adolescents during the first year of the pandemic, though findings of microbiologic testing cannot confirm a direct link with SARS-CoV-2 infection in most cases. Patient characteristics did not change between the two time periods. Difficulty accessing primary-care facilities during the pandemic in Spain may have played a role in this increase.

TITLE: Parálisis facial periférica en población pediátrica durante la pandemia de la COVID-19.Objetivos. Durante la pandemia de la COVID-19 se ha descrito una mayor frecuencia de parálisis facial periférica en adultos y niños. La etiología no está clara, ya que la mayoría de los casos ocurrió en pacientes negativos en las pruebas microbiológicas para confirmar infección por el SARS-CoV-2. Pacientes y métodos. Es un estudio retrospectivo de casos pediátricos de parálisis facial periférica atendidos el primer año de la pandemia en el servicio de urgencias de un hospital pediátrico ubicado en una de las zonas con mayor prevalencia de COVID-19 en España. Los casos de este período se comparan con los casos de los tres años anteriores. Resultados. Se incluyó a 29 pacientes. En los tres años anteriores, 24 pacientes presentaron la misma enfermedad, lo que supone que los casos se triplicaron. No se encontraron diferencias entre períodos, salvo que menos pacientes recibieron corticoides durante la pandemia (13,8 frente a 41,6%; p = 0,022). Catorce niños se sometieron a pruebas microbiológicas para detectar infección activa por el SARS-CoV-2 (12 reacciones en cadena de la polimerasa y dos test rápidos de antígenos), y todas fueron negativas. En 13 pacientes se realizó serología, y dos presentaron inmunoglobulina G positiva (15,3%). Conclusión. Se observó un aumento significativo de los casos de parálisis facial periférica en niños y adolescentes durante el primer año de la pandemia, aunque las pruebas microbiológicas no pueden confirmar un vínculo directo con la infección por el SARS-CoV-2 en la mayoría de los casos. Las características de los pacientes no cambiaron entre los dos períodos. La dificultad para acceder a los centros de atención primaria durante la pandemia pudo influir en este aumento.

[Tuberous sclerosis complex: analysis of areas of involvement, treatment progress and translation to routine clinical practice in a cohort of paediatric patients]. / Complejo esclerosis tuberosa: análisis de los ámbitos de afectación, progreso en el tratamiento y traslación a la práctica clínica habitual en una cohorte de pacientes pediátricos.

INTRODUCTION: Tuberous sclerosis complex (TSC) displays great phenotypic variability. Increasingly early diagnosis, including prenatal identification, entails the need for the paediatrician and neuropaediatrician to establish early suspicion and identification of factors that may influence prognosis and treatment. AIM: To determine the clinical criteria for early diagnosis, initial complementary tests, actions and treatments to prevent different comorbidities, so as to improve the prognosis of these patients. PATIENTS AND METHODS: Descriptive, retrospective study of = 18-year-olds with a definitive diagnosis of TSC in a tertiary hospital from 1998 to 2019. We collected variables referring to epidemiological data, multisystem involvement, complementary tests and genetics. RESULTS: Ninety-four patients were analysed. The main diagnostic reasons were epilepsy and rhabdomyomas. The frequency of occurrence of clinical criteria was determined, and neuropathological findings were the main findings, followed by cutaneous stigmata, rhabdomyomas and renal lesions. Statistical relationships were found between clinical, radiological and genetic aspects, the influence of preventive activities on the occurrence of epilepsy and the relevance of everolimus use were tested. CONCLUSIONS: Rhabdomyomas and skin stigmata in patients and parents are major diagnostic signs in infants. Tubers and subependymal nodules are statistically associated with the development of epilepsy. Early epileptic spasms, refractory to treatment in the first months, increase the risk of cognitive deficits and autism spectrum disorder. Epileptic abnormalities need to be closely monitored in the first year of life. Everolimus is an alternative treatment for several comorbidities, but its early use (< 3 years) requires further study.

TITLE: Complejo esclerosis tuberosa: análisis de los ámbitos de afectación, progreso en el tratamiento y traslación a la práctica clínica habitual en una cohorte de pacientes pediátricos.Introducción. El complejo esclerosis tuberosa (CET) presenta gran variabilidad fenotípica. El diagnóstico cada vez más precoz, incluyendo la identificación prenatal, conlleva la necesidad de establecer una sospecha e identificación temprana, por parte del pediatra y del neuropediatra, de factores que pueden influir en su pronóstico y tratamiento. Objetivo. Determinar los criterios clínicos de un diagnóstico precoz, las pruebas complementarias iniciales, las actuaciones y los tratamientos que prevengan diferentes comorbilidades, mejorando el pronóstico de estos pacientes. Pacientes y métodos. Estudio descriptivo, retrospectivo de = 18 años con diagnóstico definitivo de CET en un hospital terciario desde 1998 hasta 2019. Se recogieron variables epidemiológicas, de afectación multisistémica, pruebas complementarias y genética. Resultados. Se analizó a 94 pacientes. Los principales motivos diagnósticos fueron la epilepsia y los rabdomiomas. Se determinó la frecuencia de aparición de los criterios clínicos, y los hallazgos neuropatológicos fueron los principales, seguidos de los estigmas cutáneos, los rabdomiomas y las lesiones renales. Se comprobaron relaciones estadísticas entre aspectos clínicos, radiológicos, genéticos, la influencia de las actividades preventivas sobre la aparición de epilepsia y la relevancia del uso de everolimús. Conclusiones. Los rabdomiomas y los estigmas cutáneos en pacientes y progenitores constituyen signos diagnósticos principales en lactantes. Los túberes y los nódulos subependimarios tienen asociación estadística con el desarrollo de epilepsia. Los espasmos epilépticos en edades precoces, refractarios a tratamiento en los primeros meses, incrementan el riesgo de déficit cognitivo y trastorno del espectro autista. Es necesario monitorizar estrechamente las anomalías epilépticas en el primer año de vida. El everolimús supone una alternativa de tratamiento en varias comorbilidades, pero su uso precoz (menor de 3 años) precisa más estudios.

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome. / Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1).

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7% vs. 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs. 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs. 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs. 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications.

BACKGROUND: Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1-C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs). METHODS: Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs. RESULTS: Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-ß dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways. CONCLUSIONS: The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.

[Syringomyelias in paediatrics: a retrospective study of 25 cases]. / Siringomielias en pediatria: estudio retrospectivo de 25 casos.

INTRODUCTION: Syringomyelia is defined as a cavity containing cerebrospinal fluid inside the spinal cord. AIM: To describe the clinical characteristics of a series of patients with syringomyelia, as well as its diagnosis and treatment. PATIENTS AND METHODS: We conducted a retrospective descriptive study by reviewing the medical records at our centre. RESULTS: We reviewed 25 patients diagnosed with syringomyelia. In five cases, the diagnosis was reached casually, and eight of them presented a previous severe pathology (tumour, bone or vascular). Two patients began with hydrocephalus and clinical signs and symptoms of intracranial hypertension and just two of them reported headaches as the only symptom. Four presented progressive scoliosis, two of them as the initial complaint, and required surgery with arthrodesis and the use of a corset, respectively. A notable feature was the earliness of the diagnosis. Most of them only presented a slight loss of strength, with normal somatosensory potentials and electromyogram. Check-ups were carried out with magnetic resonance. Eight patients required a decompressive craniectomy with posterior C1-C2 laminectomy, with drainage of the syringomyelic cavity in four cases. Nine of them required a bypass valve and a ventriculostomy also had to be performed in two of them. CONCLUSIONS: The presence of syringomyelia is rare in paediatric patients, and is generally associated with malformations in the posterior fossa and a medical history of spinal dysrhaphism. Progressive scoliosis stands out as a possible isolated manifestation. A multidisciplinary approach with regular radiological check-ups and evaluation by paediatric neurology and neurosurgery services are mandatory for its follow-up.

TITLE: Siringomielias en pediatria: estudio retrospectivo de 25 casos.Introduccion. Se define siringomielia como una cavidad que contiene liquido cefalorraquideo dispuesta en el interior de la medula espinal. Objetivo. Describir las caracteristicas clinicas de una serie de pacientes con siringomielia, su diagnostico y tratamiento. Pacientes y metodos. Estudio descriptivo retrospectivo realizado mediante la revision de historias clinicas en nuestro centro. Resultados. Se revisaron 25 pacientes diagnosticados de siringomielia. En cinco el diagnostico fue casual y ocho presentaban una patologia grave previa (tumoral, osea o vascular). Dos pacientes comenzaron con hidrocefalia y clinica de hipertension intracraneal y unicamente dos destacaban cefalea como unico sintoma. Cuatro presentaron escoliosis progresiva, dos de ellos como queja inicial, y precisaron cirugia con artrodesis y uso de corse, respectivamente. Destaca la precocidad del diagnostico. La mayoria presentaba unicamente perdida de fuerza leve, con potenciales somatosensoriales y electromiograma normales. En todos se hicieron controles con resonancia magnetica. Ocho pacientes precisaron craniectomia descompresiva con laminectomia posterior C1-C2, con drenaje de la cavidad siringomielica en cuatro. Nueve requirieron valvula de derivacion y dos precisaron, ademas, ventriculostomia. Conclusiones. La presencia de siringomielia en pediatria es rara, y se asocia generalmente a malformaciones en la fosa posterior y antecedentes de disrafismo espinal. Destaca la escoliosis progresiva como posible manifestacion aislada. Un abordaje multidisciplinar con controles radiologicos seriados y la valoracion por servicios de neurologia y neurocirugia pediatricos son mandatorios para su seguimiento.

Non Hodgkin's lymphomas following chemoradiotherapy for Hodgkin's disease. Two new cases and a review of the literature.

Two patients developed non-Hodgkin's lymphoma (NHL) six and ten years after radiotherapy and chemotherapy for Hodgkin's disease nodular sclerosis type. The histological classification of the developing NHL for the two patients was: IgG (K) secreting lymphoplasmacytoid lymphoma of the stomach, and immunoblastic lymphoma of the cervical lymph nodes. Both patients responded well to conventional chemotherapy for NHL and are alive 22 and 5 months after the diagnosis of the secondary tumor. Forty eight cases of NHL after treatment for HD have been previously reported. We present a review of the literature of these cases, adding to this literature the first reported case of gastric lymphoplasmacytoid lymphoma under such circumstances.

Immunophenotypic characterisation of acute leukaemia after polycythemia vera.

AIMS: To analyze the immunophenotype of blast cells in patients with acute leukaemia after polycythemia vera, together with the most relevant clinical and haematological disease characteristics. METHODS: The immunophenotype was analysed in nine patients by immunofluorescence flow cytometry using a panel of 15 monoclonal antibodies. The DNA content of blast cells was determined using Vindelov's technique. RESULTS: The most relevant clinical and haematological disease characteristics included: the presence of enlarged spleen and liver by 56% and 67%, respectively; a moderate degree of leucocytosis with thrombocytopenia while haemoglobin was normal in 50% of patients. All patients received alkylating agents or hydroxyurea, or both. Interestingly, the chronic phase in patients receiving this latter drug was shorter. All cases showed a myeloid phenotype, four of them reactive only to early myeloid antigens (CD13/33); in the remaining cases the blast cells displayed granulomonocytic (CD14+, CD15+), erythroid (CD71 ), or megakaryocytic (CD61+, CD41+) markers. Coexpression of lymphoid related antigens (CD7, TdT, or CD19) was also detected. The morphological assessment of blast cells agreed with the immunophenotyping in five out of the nine cases. Blast cells from all six patients analysed displayed a diploid DNA content and the proportion of S-phase cells ranged from 0.4% to 4%. CONCLUSIONS: These findings suggest a pluripotential stem cell with myeloid commitment as the target cell of acute leukaemia after polycythemia vera.

Free cholesterol fiber-optic biosensor for serum samples with simplex optimization.

An optical fiber biosensor for free cholesterol monitoring in serum samples is described. Silicone-entrapped tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) complex, the luminescence of which is sensitive to oxygen changes, is used as an optical transducer of the oxidation of cholesterol by cholesterol oxidase. The biocatalyst is entrapped in a graphite powder layer deposited onto the dyed silicone film. Optimization of some interdependent chemical variables which affect the performance of the biosensor has been achieved by application of a super-modified simplex method. The dynamic range of the biosensing membranes is found to be 0.15-3.0 mM of free cholesterol. Studies of the reproducibility, stability and interferences of the device, as well as the application of the sensor to measurements in serum samples, are reported. Simplex optimization has proven to be a very useful tool in the search for the optimal conditions for performing analyses with the optical fiber biosensor.

Complex karyotype including 14q+ marker in a case of Waldenström's macroglobulinemia.

We describe a case of Waldenström's macroglobulinemia with a complex karyotype including a 14q+ marker. Secondary changes affected chromosomes 2, 4, 6, 7, 8, and 17. The cytogenetic significance of the changes and their prognostic value, as compared with those described in previous reports, are discussed.

Incidence of non-Hodgkin's lymphoma in patients treated for Hodgkin's disease.

The purpose of this study was to evaluate the incidence of non-Hodgkin's lymphoma (NHL) as a second tumor in patients treated for Hodgkin's disease (HD), as well as to establish the role of different variables in its appearance. Between January 1973 and June 1988, 101 patients with HD were treated according to the stage, with chemotherapy and/or radiotherapy. Complete remission was obtained in 87 patients. Five patients developed secondary NHL between the 77th and 124th month of complete remission. The median follow up was 73 months (range 3-227 months). The incidence of second NHL in our series was, 0%, 4.6% (CI 0-11%) and 17% (CI 4-32%) at 5, 10 and 15 years respectively. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, splenectomy, histology, stage and treatment modality) showed that the only statistically significant variable was the treatment received (p < 0.01). Cumulative incidence of NHL at 15 years, ranged from 0% for patients treated with radiotherapy or chemotherapy alone to 39.6% for those who received combined therapy (p = 0.002). We can conclude that the use of chemotherapy plus radiotherapy for treatment of HD increases the risk for the development of second NHL.

Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states.

Hypercoagulable states can be detected by measuring activation peptides, enzyme-inhibitor complexes, and fibrin/fibrinogen degradation products, which are markers of hemostatic activation. A series of these prethrombotic markers has been evaluated in the elderly, pregnancy, diabetes and acute myocardial infarction patients (n=30 in each group) as well as in hematologic malignancies (n=42). The parameters assayed were: prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA), plasmin-alpha2 antiplasmin complexes (PAP) and D-Dimer. Results were compared with those obtained in a group of 30 healthy subjects. We found a significant increase of F1+2, TAT and FPA in elderly (p<0.05), acute myocardial infarction (AMI) (p<0.01), hematologic malignancies (p<0.01), and pregnancy (p<0.0001), indicating a marked clotting activation. Diabetic patients under strict metabolic control only presented a moderate increase of TAT (p<0.05), suggesting a slight activation. We also observed a highly significant elevation of PAP and D-Dimer in elderly (p<0.001), AMI (p<0.0001), and malignancy (p<0.0001), indicating an activation of the fibrinolytic system. The combination of selected fibrinolytic and coagulation measurements is useful for the detection of a hypercoagulable state in conditions characterized by a risk of thrombosis.

Clotting activation and impairment of fibrinolysis in malignancy.

Different coagulation and fibrinolysis parameters were investigated in 149 patients with metastatic and non-metastatic tumours and results were compared with those obtained in a healthy population. Results showed a significant increase of thrombin-antithrombin complexes, fibrinopeptide A (FPA) and fibrin monomers in the group of patients (p less than 0.001). There was also a significant prolongation of euglobulin lysis time (p less than 0.005) and an increase of plasminogen activator inhibitor activity (p less than 0.0001), fibrinogen degradation products (p less than 0.001), and D-dimer (p less than 0.05) in the group of patients as compared to controls; FPA levels were also increased in patients with metastases (p less than 0.005). This study demonstrates clotting activation, at the level of fibrinogen to fibrin conversion, and impairment of fibrinolysis in patients with malignancy.

Fibrinogen Sevilla, a congenital dysfibrinogenemia characterized by an abnormal monomer aggregation and a defective plasmin lysis.

A dysfibrinogenemia (fibrinogen Sevilla) was detected in a 64-yr-old woman with no previous history of hemorrhagic diathesis or thrombosis. Thrombin and reptilase times were prolonged. The aggregation of fibrin monomers showed a prolonged latency time with a defective slope although fibrinopeptide release and clot stabilization were found to be normal. Plasmin proteolysis was abnormal with a much slower plasmic degradation in patient's purified fibrinogen. By chromatofocussing the patient's fibrinogen showed an abnormality in pattern elution with a second peak eluting at a pH slightly more basic than the normal one (pH 5.5). Likewise, the isoelectrofocussing of purified non-reduced patient's fibrinogen in agarose gel showed an abnormal distribution in its focussed bands, especially in a group which focussed in a pI-interval between 5.20-5.85. By two-dimensional electrophoresis we did not find any abnormality in the fibrinogen-reduced chains. These results could indicate that the abnormal monomer aggregation, as well as the defective plasmin lysis, could be due to conformational aspects of fibrinogen rather than to structural defects.

Fibrinogen and fibrin degradation products in patients undergoing open-heart surgery.

We have determined fibrinogen and fibrin degradation products (FgDP and FbDP respectively) by an ELISA method using specific monoclonal antibodies in 100 patients undergoing cardiopulmonary bypass (CPB) for valvular heart disease and in 60 patients undergoing aorto-coronary bypass surgery. Blood samples were taken pre-operatively and on post-operative days 1 and 5. Post-operative evolution was similar in both patient groups, with a significant increase in FgDP on post-operative days 1 and 5 with respect to baseline value (P less than 0.01). FbDP were also significantly higher on post-operative days 1 and 5 (P less than 0.001), especially the day after surgery in patients with valvular disease as compared with coronary patients (P less than 0.01). Our results indicate that fibrinolysis is more important than fibrinogenolysis after open-heart surgery, which may have pathophysiological implications.