Admisiones en los servicios de urgencias y costes económicos relacionados con procesos susceptibles de atención ambulatoria en adultos mayores que viven en centros residenciales / Emergency department admissions and economic costs burden related to ambulatory care sensitive conditions in older adults living in care homes

Objetivos Evaluar la frecuencia de las admisiones en los servicios de urgencias (ASU) por ambulatory care sensitive conditions (ACSC) y no-ACSC de personas que viven en residencias; describir y comparar sus características, y analizar los costes asociados. Método Este estudio multicéntrico, retrospectivo y observacional evaluó 2.444ASU de personas ≥65 años que viven en residencias en 5 servicios de urgencias de Cataluña por ACSC y no-ACSC, en 2017. Se recogieron variables sociodemográficas, estado funcional y cognitivo, e información sobre diagnóstico y hospitalización. Se evaluaron los costes relacionados con ACSC-ASU y se efectuó un análisis de sensibilidad utilizando diferentes supuestos de disminución de ingresos por ACSC. Resultados La media de edad de la muestra del estudio fue de 85,9 años (desviación estándar: 7,2 años). La frecuencia de ACSC-ASU y no-ACSC-ASU fue del 56,6 y el 43,4%, respectivamente. El 56,6 y el 78% presentaban dependencia severa y deterioro cognitivo, respectivamente, sin observarse diferencias entre los 2 grupos. Las 3 ACSC más frecuentes fueron caídas/traumatismos (13,8%), enfermedad pulmonar obstructiva crónica/asma (11,4%) e infección urinaria (7,4%). El coste medio por ACSC-ASU fue de 1.408,24€. Suponiendo una reducción del 60% de las ACSC-ASU, el ahorro de costes estimado sería de 1,2 millones de euros. Conclusiones Las admisiones en urgencias por ACSC procedentes de entornos residenciales suponen un impacto significativo tanto en la frecuencia como en los costes. La disminución de estas enfermedades mediante la aplicación de intervenciones específicas podría redirigir los costes evitados hacia la mejora del apoyo asistencial en los entornos residenciales (AU)

Objectives To assess the frequency of emergency department admissions (EDAs) for ambulatory care sensitive conditions (ACSC) and non-ACSC among older adults living in care homes (CH), to describe and compare their demographic and clinical characteristics, the outcomes of the hospitalization process and the associated costs. Method This multicenter, retrospective and observational study evaluated 2444 EDAs of older adults ≥65 years old living in care homes in five emergency departments in Catalonia (Spain) by ACSC and non-ACSC, in 2017. Sociodemographic variables, prior functional and cognitive status, and information on diagnosis and hospitalization were collected. Additionally, the costs related with the EDAs were calculated, as well as a sensitivity analysis using different assumptions of decreased admissions due to ACSC Results A total of 2444 ED admissions were analyzed. The patients’ mean (SD) age was 85.9 (7.2) years. The frequency of ACSC-EDA and non-ACSC-EDA was 56.6% and 43.4%, respectively. Severe dependency and cognitive impairment were present in 56.6% and 78%, respectively, with no differences between the two groups. The three most frequent ACSC were falls/trauma (13.8%), chronic obstructive pulmonary disease/asthma (11.4%) and urinary tract infection (7.4%). The average cost per ACSC-EDA was €1408.24. Assuming a 60% reduction of ACSC-EDA, the estimated cost savings would be €1.2 million. Conclusions Emergency admissions for ACSC from care homes have a significant impact on both frequency and costs. Reducing these conditions through targeted interventions could redirect the avoided costs toward improving care support in residential settings (AU)

Emergency department admissions and economic costs burden related to ambulatory care sensitive conditions in older adults living in care homes.

OBJECTIVES: To assess the frequency of emergency department admissions (EDA) for ambulatory care sensitive conditions (ACSC) and non-ACSC among older adults living in care homes (CH), to describe and compare their demographic and clinical characteristics, the outcomes of the hospitalisation process and the associated costs. METHOD: This multicenter, retrospective and observational study evaluated 2444 EDAs of older adults ≥ 65 years old living in care homes in 5 emergency departments in Catalonia (Spain) by ACSC and non-ACSC, in 2017. Sociodemographic variables, prior functional and cognitive status, and information on diagnosis and hospitalisation were collected. Additionally, the costs related with the EDAs were calculated, as well as a sensitivity analysis using different assumptions of decreased admissions due to ACSC. RESULTS: A total of 2444 ED admissions were analysed. The patients' mean (SD) age was 85.9 (7.2) years. The frequency of ACSC-EDA and non-ACSC-EDA was 56.6% and 43.4%, respectively. Severe dependency and cognitive impairment were present in 56.6% and 78%, respectively, with no differences between the two groups. The three most frequent ACSC were falls/trauma (13.8%), chronic obstructive pulmonary disease/asthma (11.4%) and urinary tract infection (7.4%). The average cost per ACSC-EDA was є1,408.24. Assuming a 60% reduction of ACSC-EDA, the estimated cost savings would be є1.2 million. CONCLUSIONS: Emergency admissions for ACSC from care homes have a significant impact on both frequency and costs. Reducing these conditions through targeted interventions could redirect the avoided costs towards improving care support in residential settings.

Obesidad secundaria a síndrome endocrinológico en paciente pluripatológica / Obesity secondary to endocrinology syndrome in a polymorbid patient

Presentamos el caso de una paciente de 64 años, natural de Rumanía, con antecedentes médicos de síndrome de apnea-hipopnea, cirrosis hepática, EPOC y artrosis. Fumadora activa de un paquete de cigarrillos/día. La paciente es remitida desde la consulta de neumología para estudio ambulatorio por presentar como hallazgo incidental adenomas suprarrenales bilaterales y aumento progresivo de peso en los últimos 5 años. En el estudio de adenomas suprarrenales y obesidad se objetiva la presencia de un síndrome de Cushing. Es importante estudiar la aparición de la obesidad reciente en una paciente pluripatológica dado que puede haber otras causas secundarias además de las enfermedades subyacentes que presenta. Durante la presentación del caso clínico se realiza un abordaje esencial y práctico de la enfermedad adrenal. (AU)

We present the case of a 64-year-old woman from Romania with a medical history of obstructive sleep apnea-hypopnea syndrome, hepatic cirrhosis, COPD, and osteoarthritis. She smokes one pack of cigarettes per day. The patient is referred from the pulmonology department for an outpatient evaluation for an incidental finding of bilateral adrenal adenomas and progressive weight gain over the last five years. Cushing syndrome is detected during study of the adrenal adenomas and obesity. It is important to study recent-onset obesity in multimorbid patients as there could be other secondary causes in addition to the underlying diseases they present with. During the presentation of this clinical case, an essential, practical approach to the adrenal pathology is made. (AU)

Obesity secondary to endocrinology syndrome in a polymorbid patient.

We present the case of a 64-year-old woman from Romania with a medical history of obstructive sleep apnea-hypopnea syndrome, hepatic cirrhosis, COPD, and osteoarthritis. She smokes one pack of cigarettes per day. The patient is referred from the pulmonology department for an outpatient evaluation for an incidental finding of bilateral adrenal adenomas and progressive weight gain over the last five years. Cushing syndrome is detected during study of the adrenal adenomas and obesity. It is important to study recent-onset obesity in multimorbid patients as there could be other secondary causes in addition to the underlying diseases they present with. During the presentation of this clinical case, an essential, practical approach to the adrenal pathology is made.

Therapeutic possibilities for urolithiasis in childhood. / Posibilidades terapéuticas de las urolitiasis en la infancia.

OBJECTIVES: We present our case studies on paediatric urolithiasis, the techniques employed in its treatment and its results. MATERIAL AND METHODS: A retrospective study of paediatric urolithiasis of the upper urinary tract (UUT) treated at our centre between 2003 and 2014. We recorded demographic, clinical, diagnostic and therapeutic data and the complications. The therapeutic plan was recorded as isolated (extracorporeal lithotripsy, ureterorenoscopy, nephrolithotomy or surgery) or combined therapy. RESULTS: We examined 41 renal/urethral units in 32 patients. The median age was 5 years (range, 11 months-14 years). The mean size was 12.9cm (±7.3mm). The locations were as follows: 23 (56%) in the renal pelvis (staghorn in 15 cases), 10 (24) in lower calyx and 8 (20%) in the urethra. We performed 80 procedures, with no differences in the age groups, which resulted in 12 complications (15%) but no septic condition secondary to lithotripsy. Stone removal from the urethra had a 100% success rate with the ureterorenoscopy. The overall cure rate was 90%. CONCLUSION: The paediatric urolithiasis approach offers multiple alternatives. It is therefore important to tailor the procedure according to the size, location and composition of the stone. In our centre, the use of paediatric extracorporeal shock wave lithotripsy is safer. Ureterorenoscopy, semirigid or flexible, provides excellent results in ureters. Percutaneous nephrolithotomy with minimal access can be performed on small children and nursing infants.

Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.

DNA methyltransferase 3A (DNMT3A) mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Transplantation studies have elucidated an important role for Dnmt3a in stem cell self-renewal and in myeloid differentiation. Here, we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Mx1-Cre-mediated Dnmt3a ablation led to the development of a lethal, fully penetrant MPN with myelodysplasia (MDS/MPN) characterized by peripheral cytopenias and by marked, progressive hepatomegaly. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. The MDS/MPN induced by Dnmt3a ablation was transplantable, including the marked hepatomegaly. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Gene expression and DNA methylation analyses of progenitor cell populations identified differential regulation of hematopoietic regulatory pathways, including fetal liver hematopoiesis transcriptional programs. These data demonstrate that Dnmt3a ablation in the hematopoietic system leads to myeloid transformation in vivo, with cell-autonomous aberrant tissue tropism and marked extramedullary hematopoiesis (EMH) with liver involvement. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo.

[Comparison of two nutritional screening tools for predicting the development of complications in hospitalized patients]. / Comparación de dos herramientas de cribado nutricional para predecir la aparición de complicaciones en pacientes hospitalizados.

BACKGROUND: The prevalence of malnutrition in hospitalized patients is high and has been associated with higher morbimortality. Currently no nutritional screening tool is considered the gold standard for identifying nutritional risk. The aims of this study were to evaluate the prevalence of nutritional risk in hospitalized patients using the nutritional screening tools Mini Nutritional Assessment (MNA) and Nutrition Risk Screenig 2002 (NRS 2002) and to identify the ability for predicting development of complications. METHODS: We evaluated 57 patients admitted within the first 48 h in different medical or surgical wards of the hospital. The patients were assessed by MNA and NRS 2002 and using anthropometric and laboratory parameters. Agreement between MNA and NRS 2002 was analyzed with the kappa index. ROC curves were used for assessing the validity of the both tools in predicting complications with determination of the area under the curve (AUC). RESULTS: The prevalence of patients at nutritional risk was 38.6% with the NRS-2002 and 49.1% with the MNA. The agreement between two tools was moderate (κ = 0.436, p = 0.001). The incidence of complications was significantly higher in patients at nutritional risk defined by the NRS 0,002) but not according to the MNA (28.6% vs. = 2002 (40.9% vs. 5.7%; p 0.08). Sensitivity for predicting complications was 81.8% with = 10.3%, p the NRS 2002 and 72.7% with the MNA and specificity was 71.7% and 56.5% respectively. By ROC curve, both tests were valid to identify the risk of complications: NRS 2002 AUC = 0.768 (confidence interval (IC) 95%: 0.637-0.869) and MNA AUC = 0.646 (IC 95%: 0.508-0.768), but the AUC was significantly higher with the NRS 2002 (p = 0.047). CONCLUSIONS: The prevalence of nutritional risk in hospitalized patients is high. NRS 2002 is a screening tool more valid than MNA to predict the development of complications.

Somatic mosaicism in a case of apparently sporadic Creutzfeldt-Jakob disease carrying a de novo D178N mutation in the PRNP gene.

Transmissible spongiform encephalopathies (TSEs) are a group of rare fatal neurodegenerative disorders. Creutzfeldt-Jakob disease (CJD) represents the most common form of TSE and can be classified into sporadic, genetic, iatrogenic and variant forms. Genetic cases are related to prion protein gene mutations but they only account for 10-20% of cases. Here we report an apparently sporadic CJD case with negative family history carrying a mutation at codon 178 of prion protein gene. This mutation is a de novo mutation as the parents of the case do not show it. Furthermore the presence of three different alleles (wild type 129M-178D and 129V-178D and mutated 129V-178N), confirmed by different methods, indicates that this de novo mutation is a post-zygotic mutation that produces somatic mosaicism. The proportion of mutated cells in peripheral blood cells and in brain tissue was similar and was estimated at approximately 97%, suggesting that the mutation occurred at an early stage of embryogenesis. Neuropathological examination disclosed spongiform change mainly involving the caudate and putamen, and the cerebral cortex, together with proteinase K-resistant PrP globular deposits in the cerebrum and cerebellum. PrP typing was characterized by a lower band of 21 kDa. This is the first case of mosaicism described in prion diseases and illustrates a potential etiology for apparently sporadic neurodegenerative diseases. In light of this case, genetic counseling for inherited and sporadic forms of transmissible encephalopathies should take into account this possibility for genetic screening procedures.

[Study of nutritional menus offered at noon school in Granada]. / Estudio de los menús escolares servidos en colegios de Granada.

OBJECTIVE: It has been considered a study of nutritional menus offered at noon School in Granada. Balanced diet in children and youth will enable the prevention of diseases in adulthood. Comparing the menus prepared on school and the services offered by catering. MATERIAL AND METHODS: The menus are aimed at 5,399 children from Granada, analyzed 354 school menus from 29 centres, public and private schools. Eleven colleges have their own kitchen, while 18 had hired a catering service. The amounts provided in each menu were estimated using standardized photographs of different sizes ration identified by those responsible for the dining room or by weighing Served directly from the ration. Nutritional assessment was determined by software, and the statistical treatment with the program SPSS v. 15.0. RESULTS: There were statistically significant differences in the intakes of energy and nutrients from the menus developed in the centres and catering services. In the catering firms, the available energy and nutrition is similar, and in the menus prepared at the centres, there are significant differences in relation to some nutrients, depending on whether public school or private. CONCLUSIONS: The energy, protein and lipid is high and low input from carbohydrates. It is the frequency of excessive consumption of meat and derivatives. To balance the diet of school, it is necessary to complement the menu of midday meals with the rest of the day.

[Walkrounds and briefings in the improvement of the patient safety]. / Walkrounds y Briefings en la mejora de la seguridad de los pacientes.

OBJECTIVE: Training, to increase the safety culture, the reporting of adverse events, and to implement improvements using WalkRounds and Briefings. MATERIAL AND METHODS: Monte Naranco Hospital, hospital with 200 beds and mainly with geriatric patients. METHOD: Patient safety surveys and evaluations of the leaders. DESIGN: face-to-face 1/2h interviews with the healthworkers (3-5 people), and in the changes of shifts from 2004-2009. Analysis tools: a) Patient safety surveys (University of Texas and Agency for Healthcare Research and Quality - AHRQ); b) WalkRounds and Briefings forms; c) classification of contributory factors, and the severity of adverse events. RESULTS: Surveys were conduted on 36.9% and 33.8% of the healthworkers, respectively). WalkRounds training: 84 healthworkers. Number of WalkRounds: with Pharmacy Service (493), and with Patient Complaints Service (147), and Briefings: 307. Reporting of adverse events: Medication errors (71.1%), equipment (7.2%), others (21.7%). Contributory factors Working environment (30.1%), work team (29.2%), others (40.7%). In the post-briefing survey 86.7% of the healthworkers thought that it was a useful tool. New needs: feedback of the personnel with control charts. CONCLUSIONS: WalkRounds and Briefings allow a higher number of adverse events (more than 20%) to be detected, and are useful for the training of healthworkers. There is better feedback and there was less problems with equipment and outpatient units. Face-to-face communication with the healthworkers is a key element in patient safety and helps to know the needs to the front line wards.

Phenotypic variability in familial prion diseases due to the D178N mutation.

BACKGROUND: Between January 1993 and December 2003, 19 patients with familial prion diseases due to the D178N mutation were referred to the regional epidemiological registry for spongiform encephalopathies in the Basque Country in Spain, a small community of some 2,100,000 inhabitants. METHODS: Ten further patients belonging to the same pedigrees were retrospectively ascertained through neurological or neuropathological records. In four of the patients, the diagnosis was confirmed by analysing DNA obtained from paraffin blocks. In this article, we report on the clinical, genetic, and pathological features of the 23 patients carrying the D178N mutation confirmed by genetic molecular analysis. Haplotyping studies suggest a founder effect among Basque born families, explaining in part this unusually high incidence of the D178N mutation in a small community. Only two patients (8%) lack familial antecedents. RESULTS: We have observed a phenotypic variability even among homozygous 129MM patients. Our findings challenge the currently accepted belief that MM homozygosity in codon 129 is always related to a fatal familial insomnia (FFI) phenotype. Indeed, seven out of 17 patients with a 129MM genotype in this series presented with a Creutzfeldt-Jakob disease (CJD) clinicopathological picture. CONCLUSIONS: The considerable clinical and pathological overlapping observed among homozygous 129MM patients favours the view that FFI and CJD178 are the extremes of a spectrum rather than two discrete and separate entities. Other genetic or environmental factors apart from the polymorphism in codon 129 may play a role in determining the phenotypic expression of the D178N mutation in the PRNP gene.

A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease.

BACKGROUND: Frontotemporal dementia with parkinsonism is often linked to chromosome 17 and is related to mutations in the MAPT gene. In some families the genetic basis is still unknown. The authors report two pedigrees with FTDP-17 harboring a novel mutation (K317M) in exon 11 in the MAPT gene. METHODS: The authors identified two apparently unrelated pedigrees with an autosomal dominant neurodegenerative condition. Thirteen patients were examined and eight autopsies were performed. RESULTS: Mean age at onset was 48 years. Mean disease duration was 6 years. Dysarthria often heralded the disease. All cases had parkinsonism and pyramidalism and half of them had amyotrophy. Behavioral or personality changes were not a prominent feature. Cognitive decline appeared late in the evolution. Neuropathologically, a massive degeneration of the substantia nigra without Lewy bodies was a constant finding. A variable degree of frontotemporal atrophy was found. Corticospinal tract degeneration and anterior horn neuron loss were present in six of seven autopsies in which the spinal cord was examined. An extensive deposition of abnormal tau protein in a mixed pattern (neuronal, glial) was observed. Pick's bodies were not seen. Biochemical analysis of tau revealed two bands of 64 and 68 kDa. CONCLUSION: Genetic analysis revealed the same novel mutation (K317M) in exon 11 of the MAPT gene in both pedigrees. A common haplotype between members of the two pedigrees suggests that they belong to the same family.

Effect of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on endochondral ossification lesions induced by a lethal oral dose of uranyl nitrate.

A 350 mg/kg body weight (b.w.) oral dose of uranyl nitrate (UN) caused 100% mortality in mice three days after administration, due to resulting kidney lesions. Mortality decreased 50% after an oral (o) or subcutaneous (sc) dose of bisodic etidronate (EHBP). Given that bone is also a target organ for uranium (U) in acute intoxication, the aim of this work was to study the effect of exposure to a lethal oral dose of UN on endochondral ossification, and the latter's response to EHBP treatment. One hundred male Balb/c mice weighing 25 g were assigned to one of ten groups. Group I served as control. Group II received a lethal 350 mg/kg b.w. oral dose of UN by gavage. Groups III, IV, VII, and VIII received an equal dose of UN immediately followed by a single 500 mg/kg oral dose of EHBP in groups III and VII and a single 50 mg/kg subcutaneous dose of EHBP in groups IV and VIII. Groups V and IX only received a single 500 mg/kg oral dose of EHBP, and groups VI and X received a single 50 mg/kg subcutaneous dose of EHBP. The animals in groups II, III, IV, V, and VI were sacrificed 48 h after the onset of the experiment, whereas those in groups VII, VIII, IX, and X were killed at 14 days. Histologic and histomorphometric studies were performed on the femurs to determine growth cartilage width, bone volume, and metaphyseal bone activity. Our results showed that all growth cartilage and metaphyseal bone histomorphometric parameters were significantly lower in animals exposed to UN at 48 h than in controls. EHPB administration was found to prevent this condition at 48 h reaching similar values to those of controls. Although histomorphometric values did not reach control values at 14 days, they were higher than those of animals exposed to UN at 48 h not treated with EHBP. It is noteworthy that these values also decreased in animals only receiving EHBP at 14 days. Our results show that EHBP effectively ameliorates the adverse effects of a lethal dose of UN on endochondral ossification.

Renal function in mice poisoned with oral uranium and treated with ethane-1-hydroxy-1,1-bisphosphonate (EHBP).

Exposure to uranium is a risk for the workers involved in uranium mining, purification, and manufacture, principally by its ingestion or inhalation. It is also a risk for the population at large in case of intake of contaminated water or food. Uranium induces nephropathy that is characteristic of heavy metals, which can lead to death. The toxic effects of uranium can be prevented by a biphosphonate, ethane-1-hydroxy-1,1-bisphosphonate (bisodic etidronate), administered orally or subcutaneously. Employing bisodic etidronate, our laboratory obtained satisfactory results in terms of survival in adult mice, adult rats, and suckling rats. The aim of the present study was to evaluate the efficacy of bisodic etidronate for preventing renal dysfunction induced by a lethal dose of uranyl nitrate, employing serum levels of urea and creatinine as end-points. Two experiments were performed over different time periods, i.e., Experiment A: 48 h, Experiment B: 14 d. Each experiment was performed with 4 groups of 20 male Balb/c mice each, 25 g average body weight. Three of these groups received 350 mg kg(-1) of body weight of uranyl nitrate by gavage (forced oral administration). Two of the three exposed groups were treated with bisodic etidronate either by gavage in a dose of 500 mg kg(-1) body weight or with a subcutaneous injection of 50 mg kg(-1) body weight. The fourth group served as control. Survivors of the experimental groups were sacrificed at the end of the experiment by overdose of inhalation anesthetic (ether). The kidneys were routinely processed for histological analysis. Blood samples were taken by cardiac puncture to assess urea and creatinine serum levels. Urea and creatinine serum levels were markedly lower at 48 h in exposed animals treated with bisodic etidronate than in untreated exposed animals. On day 14 these values in exposed and treated animals did not differ significantly from control values. The renal function of animals treated with orally or subcutaneous bisodic etidronate that survived uranyl nitrate exposure was markedly improved compared to the controls of untreated exposed animals at 48 h. At 14 days, treatment with bisodic etidronate averted renal damage. At this time, the histologic study of kidneys showed images of tissue recovery. These results suggest that the use of EHBP may be of great value in reducing the renal damage.

Neumomediastino y enfisema cervical en cirugía maxilofacial / Pneumodemiastinum and cervical emphysema in maxillofacial surgery

La aparición de un neumomediastino asociado a enfisema subcutáneo cervical es una rara complicación en los pacientes a los que se practican cirugías de la región cérvicofacial. Se presentan 3 casos, cada uno de ellos con una causa diferente; en dos se desencadenó neumomediastino tras enfisema subcutáneo cervical, por vía descendente, y el otro se debió a barotrauma pulmonar intraoperatorio. Debido a que se trata de una causa potencial de complicaciones se recomienda cobertura antibiótica profiláctica. (AU)

Afectación ósea de linfoma

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p16 Expression in squamous carcinomas of the tongue.

BACKGROUND: 81 patients with tongue carcinomas were studied to determine: 1). the proportion of carcinomas with altered p16 expression; 2). whether loss of p16 is an early carcinogenic event; 3). whether p16 expression alterations influence the prognosis. METHODS: 50/81 cases could be analysed by immunohistochemistry. RESULTS: Tumours were p16- in 32% (16/50) and p16+ in 68% (34/50) of patients; 32.3% (11/34) of p16+ tumours presented 1-10% of tumour cells as positive, 14.7% (5/34) 11-40% as positive, and 59.2% (18/34) presented 41-100% of tumour cells as positive. Adjacent nontumoural epithelium (ANTE) was available in 33 of the 50 immunohistochemically analysed specimens. ANTE was normal in 25 cases and dysplastic in 8 cases. In normal ANTE, p16 expression was positive in 16% (4/25) and negative in 84% (21/25) of cases. p16 expression was negative in all dysplastic ANTE samples (8/8). CONCLUSIONS: Changes in p16 expression are frequent in tongue cancer and can be detected at very early stages of carcinogenesis. Nevertheless, in our study neither the absence nor the degree of p16 expression influenced the survival of patients.

Orally administered ethane-1-hydroxy-1,1-biphosphonate reduces the lethal effect of oral uranium poisoning.

Intoxication with uranium compounds is both an occupational risk for the workers engaged in the different processes of the elaboration of nuclear fuel and a risk for the population at large in terms of contaminated water and food. The toxic effects of uranium can be reduced by the administration of a biphosphonate, ethane-1-hydroxy-1,1-biphosphonate (EHBP), subcutaneously or intraperitoneally. The aim of the present work was to examine whether orally administered EHBP reduces the lethal effect of a single orally administered toxic dose of uranyl nitrate. Nine groups of 20 male Balb-c mice were used. Five groups received 350 mg kg(-1) of uranyl nitrate orally administered by gavage, four were co-treated 20 min later with EHBP either by gavage (350, 500, or 700 mg kg(-1)) or by subcutaneous injection (50 mg kg(-1)), and one group was not treated. Four groups of animals received only EHBP in doses and routes the same as those used in the intoxicated animals. Survival was assessed for 14 d. On day 14 the surviving animals of all groups were killed. An additional group of uranium intoxicated animals was killed on day 2 after the start of the experiment. Kidneys were examined histologically. On day 3 all the animals treated with uranyl nitrate alone and 20% of the animals treated with 700 mg kg(-1) of EHBP alone were dead. Survival at day 14 of the groups of mice intoxicated with uranyl nitrate and treated with EHBP (50 mg kg(-1) orally or 50 mg kg(-1) subcutaneously) was 45.0 and 49.6%, respectively. Tubule necrosis lesions were present in kidneys of mice intoxicated with uranyl nitrate, whereas lesions were less severe in mice treated with EHBP. Oral administration of EHBP is effective for reducing the lethal effect of uranium, and it is at least as useful as subcutaneous administration for prompt therapy of oral uranium exposure, achieving a survival rate of almost 50%.