RESUMEN
The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.
Asunto(s)
Riñón , Proteínas de Transporte de Membrana , Ratones , Animales , Riñón/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Equilibrio Ácido-Base/fisiología , Nefronas/metabolismo , Transportadores de Sulfato/metabolismo , Bicarbonatos/metabolismo , Antiportadores de Cloruro-BicarbonatoRESUMEN
Freeze-casting consists of freezing a liquid suspension (aqueous or other), followed by sublimation of the solidified state to the gas state under reduced pressure, and subsequent sintering of the remaining scaffold to consolidate and densify the struts and walls. The structure is very porous with the pores being a replica of the solvent crystals. The technique is rather versatile and the use of a liquid solvent (water most of the time) as a pore forming agent is a strong asset. Freeze-casting has also been developed as a near net shape forming route yielding dense ceramics. In this work we report on porous composite materials synthesized via the ice templating method. Poly(vinyl alcohol) (PVA) is used as matrix and nano-silica (SiO2), nanoclay (NC) and microfibrillated cellulose (MFC) are used as fillers to improve the mechanical stability of the PVA scaffold. We show our results on the porosity and mechanical stability and consider these porous nanocomposites as potential insulation materials with low thermal conductivity and superior mechanical properties.
RESUMEN
Infection with methicillin-resistant Staphylococcus aureus (MRSA) occurs in both the inpatient and outpatient sector. The reimbursement for diagnostic services and eradication therapy in the outpatient sector was regulated for the first time on 01.04.2012 and after a 2-year test period, has been adopted into the standard range of care services. The aim of this retrospective study was to give an overview of the current situation in services and reimbursement in Germany and describe MRSA patients and their treatment in the outpatient sector. Secondary data, namely reimbursement data of the National Association of Statutory Health Insurance Physicians (KBV) und the Physicians' Association (KV) Mecklenburg-West Pomerania for the period 01/04/2012-31/03/2014 were analyzed. Results show that on the federal level, MRSA services amounting to 3,235,870.18 have been reimbursed and that diagnostic costs exceed treatment costs. In Germany, 5,627 doctors invoiced services related to MRSA; 51,56% of these were general practitioners and 21,25% specialists in internal medicine working in general practice. In the KV Mecklenburg-Western Pomerania, patients were elderly (average age 69,13), cost for services were on average 27,76 , and 76,85% of the patients were treated within one quarter. On the whole, there were regional differences in the identification and eradication of MRSA in the outpatient setting. In order to provide an extended base for a more efficient resource allocation in the health care sector, in addition to analysis of MRSA eradication from the medical point of view, attention needs to be paid to patient flow between the out- and inpatient sectors, as well as economic aspects.
Asunto(s)
Atención Ambulatoria/economía , Portador Sano/economía , Servicios Contratados/economía , Staphylococcus aureus Resistente a Meticilina , Programas Nacionales de Salud/economía , Mecanismo de Reembolso/economía , Infecciones Estafilocócicas/economía , Antibacterianos/economía , Antibacterianos/uso terapéutico , Técnicas Bacteriológicas/economía , Portador Sano/diagnóstico , Portador Sano/tratamiento farmacológico , Trazado de Contacto/economía , Honorarios Médicos , Alemania , Pruebas de Sensibilidad Microbiana/economía , Factores de Riesgo , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
We here report a family from Libya with three siblings suffering from early onset achalasia born to healthy parents. We analyzed roughly 5000 disease-associated genes by a next-generation sequencing (NGS) approach. In the analyzed sibling we identified two heterozygous variants in CRLF1 (cytokine receptor-like factor 1). Mutations in CRLF1 have been associated with autosomal recessive Crisponi or cold-induced sweating syndrome type 1 (CS/CISS1), which among other symptoms also manifests with early onset feeding difficulties. Segregation analysis revealed compound heterozygosity for all affected siblings, while the unaffected mother carried the c.713dupC (p.Pro239Alafs*91) and the unaffected father carried the c.178T>A (p.Cys60Ser) variant. The c.713dupC variant has already been reported in affected CS/CISS1 patients, the pathogenicity of the c.178T>A variant was unclear. As reported previously for pathogenic CRLF1 variants, cytokine receptor-like factor 1 protein secretion from cells transfected with the c.178T>A variant was severely impaired. From these results we conclude that one should consider a CRLF1-related disorder in early onset achalasia even if other CS/CISS1 related symptoms are missing.
Asunto(s)
Anomalías Múltiples/genética , Acalasia del Esófago/genética , Deformidades Congénitas de la Mano/genética , Hiperhidrosis/genética , Receptores de Citocinas/genética , Trismo/congénito , Anomalías Múltiples/fisiopatología , Muerte Súbita , Acalasia del Esófago/fisiopatología , Facies , Predisposición Genética a la Enfermedad , Deformidades Congénitas de la Mano/fisiopatología , Secuenciación de Nucleótidos de Alto Rendimiento , Homocigoto , Humanos , Hiperhidrosis/fisiopatología , Mutación , Linaje , Trismo/genética , Trismo/fisiopatologíaRESUMEN
Endoplasmic reticulum (ER) stress, defective autophagy and genomic instability in the central nervous system are often associated with severe developmental defects and neurodegeneration. Here, we reveal the role played by Rint1 in these different biological pathways to ensure normal development of the central nervous system and to prevent neurodegeneration. We found that inactivation of Rint1 in neuroprogenitors led to death at birth. Depletion of Rint1 caused genomic instability due to chromosome fusion in dividing cells. Furthermore, Rint1 deletion in developing brain promotes the disruption of ER and Cis/Trans Golgi homeostasis in neurons, followed by ER-stress increase. Interestingly, Rint1 deficiency was also associated with the inhibition of the autophagosome clearance. Altogether, our findings highlight the crucial roles of Rint1 in vivo in genomic stability maintenance, as well as in prevention of ER stress and autophagy.
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Autofagia , Encéfalo/metabolismo , Estrés del Retículo Endoplásmico , Inestabilidad Genómica , Proteínas Supresoras de Tumor/genética , Proteínas de Transporte Vesicular/genética , Animales , Apoptosis , Encéfalo/citología , Células Cultivadas , Ratones de la Cepa 129 , Ratones Transgénicos , Mitosis , Células-Madre Neurales/fisiología , Cultivo Primario de Células , Células de Purkinje/fisiología , Proteínas Supresoras de Tumor/metabolismo , Proteínas de Transporte Vesicular/metabolismoRESUMEN
UNLABELLED: Congenital factor VII (FVII) and factor X (FX) deficiencies belong to the group of rare bleeding disorders which may occur in separate or combined forms since both the F7 and F10 genes are located in close proximity on the distal long arm of chromosome 13 (13q34). We here present data of 192 consecutive index cases with FVII and/or FX deficiency. 10 novel and 53 recurrent sequence alterations were identified in the F7 gene and 5 novel as well as 11 recurrent in the F10 gene including one homozygous 4.35 kb deletion within F7 (c.64+430_131-6delinsTCGTAA) and three large heterozygous deletions involving both the F7 and F10 genes. One of the latter proved to be cytogenetically visible as a chromosome 13q34 deletion and associated with agenesis of the corpus callosum and psychomotor retardation. CONCLUSIONS: Large deletions play a minor but essential role in the mutational spectrum of the F7 and F10 genes. Copy number analyses (e. g. MLPA) should be considered if sequencing cannot clarify the underlying reason of an observed coagulopathy. Of note, in cases of combined FVII/FX deficiency, a deletion of the two contiguous genes might be part of a larger chromosomal rearrangement.
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Deficiencia del Factor VII/epidemiología , Deficiencia del Factor VII/genética , Factor VII/genética , Deficiencia del Factor X/epidemiología , Deficiencia del Factor X/genética , Factor X/genética , Adolescente , Adulto , Anciano , Deficiencia del Factor VII/congénito , Deficiencia del Factor X/congénito , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
Aim of this study was to determine the additional expenditures for a German statutory health insurance which are induced by patients with multi-resistant bacteria. Therefore a nationwide cross-sectional data analysis using routine data of the health insurance "Techniker Krankenkasse" was conducted. In the consideration of costs we included expenditures for inpatient and outpatient care and on drugs in a time period of 12 months. A control group was matched by age, gender, basic disease, quarterly period and region. On average additional costs of 17,500 Euro per insured were calculated due to the presence of multi-resistant bacteria. The hypothesis was corroborated in that the level of these costs differ widely by age, gender and basic disease.
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Antibacterianos/economía , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/economía , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Costos de la Atención en Salud/estadística & datos numéricos , Programas Nacionales de Salud/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria/estadística & datos numéricos , Antibacterianos/uso terapéutico , Infecciones Bacterianas/epidemiología , Niño , Preescolar , Costo de Enfermedad , Unión Europea , Femenino , Alemania/epidemiología , Encuestas de Atención de la Salud , Hospitalización/economía , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: The aim of our clinical study was to correlate liver function measured by indocyanine green (ICG) elimination and clinical outcomes in patients with an early stage of community-acquired sepsis (CAS). MATERIALS AND METHODS: A total of 341 patients (≥ 18 years) presenting with suspicion of CAS or evidence of an infection and fulfillment of ≥ 2 systemic inflammatory response syndrome (SIRS) criteria were included in the observational study"Prognosis of early sepsis 2" (Prognose der frühen Sepsis 2, ProFS 2). Patients who had been hospitalized within the last 7 days were excluded. In a subgroup of these patients (n = 72) who were transferred to an intensive or intermediate care unit according to the clinical judgment of the treating physicians, ICG elimination (plasma disappearance rate, ICG-PDR; 15 min retention rate, ICG-R15) was assessed by using a noninvasive monitoring system (LiMON, PULSION Medical Systems, Germany). ICG-PDR and -R15 were determined on the day of admission (n = 72) and after 96 h (n = 34). The primary end point of the study was defined as death within 30 days. Secondary endpoints were need for renal replacement therapy, requirement for invasive mechanical ventilation, and length of stay in an intermediate or intensive care unit. RESULTS AND CONCLUSION: In contrast to patients with sepsis or severe sepsis, ICG elimination was found to be significantly impaired in patients with septic shock. Furthermore, a significant predictive value of ICG-PDR and -R15 on the day of admission for the need for subsequent renal replacement therapy (n = 12) was observed. In addition, reduced ICG elimination was associated with a longer stay in an intermediate or intensive care unit. However, ICG elimination on admission could not predict 30-day mortality (n = 14) or requirement of mechanical ventilation (n = 20).
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Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/diagnóstico , Verde de Indocianina/farmacocinética , Pruebas de Función Hepática/métodos , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Anciano , Anciano de 80 o más Años , Infecciones Comunitarias Adquiridas/mortalidad , Determinación de Punto Final , Femenino , Alemania , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Masculino , Tasa de Depuración Metabólica/fisiología , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estadística como Asunto , Síndrome de Respuesta Inflamatoria Sistémica/mortalidadRESUMEN
Infections with methicillin-resistant Staphylococcus aureus (MRSA) are assumed to have a high economic impact due to increased hygienic measures and prolonged hospital length of stay. However, surveys on the real expenditure for the prevention and treatment of MRSA are scarce, in particular with regard to the German Diagnosis-Related Groups (G-DRG) payment system. The aim of our study is to empirically assess the additional cost for MRSA management measures and to identify the main cost drivers in the whole process from the hospital's point of view. We conducted a one-year retrospective analysis of MRSA-positive cases in a German university hospital and determined the cost of hygienic measures, laboratory costs, and opportunity costs due to isolation time and extended lengths of stay. A total of 182 cases were included in the analysis. The mean length of hospital stay was 22.75 days and the mean time in isolation was 17.08 days, respectively. Overall, the calculated MRSA-attributable costs were
Asunto(s)
Manejo de Caso/economía , Hospitalización/economía , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/economía , Infecciones Estafilocócicas/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Alemania , Hospitales Universitarios , Humanos , Lactante , Tiempo de Internación , Masculino , Persona de Mediana Edad , Aislamiento de Pacientes/economía , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Hand hygiene has been acknowledged as the single most important measure to prevent nosocomial infections. Likewise, for non-clinical settings, hand hygiene is recognized as a key element to prevent the spread of infectious diseases, nevertheless poor compliance has been documented. The feasibility of hand hygiene interventions in open-community settings with adults is mostly unclear. AIM: To investigate the acceptability and feasibility of a health campaign to promote hand hygiene with alcohol-based hand disinfectants at workplaces in a non-clinical setting. METHODS: The surveys were conducted as part of a prospective, controlled intervention study with volunteers from the administration of the Ernst-Moritz-Arndt-University Greifswald, the municipality of Greifswald and the state of Mecklenburg-West Pomerania. Participants in the intervention group were provided with alcohol-based hand disinfection; the control group was unchanged. Eleven volunteers filled out an initial survey at the beginning of the intervention regarding demographic and health-related questions as well as questions about the type of work, and a survey after completion of the intervention to evaluate the study's impact on the participants' attitudes toward hand hygiene. Participants in the experimental group filled out a monthly questionnaire regarding their compliance with hand hygiene measures, feasibility of hand disinfection and possible side-effects. FINDINGS: From 850 employees asked to participate, 134 were included in the study, and surveys from 129 participants (intervention: 64 vs control: 65) were accepted for analysis. Overall, datasets of 1230 person-months (79.46% of total possible follow-up surveys) were collected. Return rate and compliance remained high during the study period. Hand disinfection did not lead to skin problems in the majority of person-months. After the intervention, a majority of participants would favour a further use of hand disinfectants. CONCLUSION: Campaigns that enforce the use of alcohol-based hand disinfectants can have a sustainable effect on the compliance with hand hygiene measures in non-clinical settings. Campaigns have been shown to be feasible and effective in the prevention of transmissible diseases, therefore employers should consider whether hand hygiene campaigns to introduce waterless hand rubs could be included in companies' health programmes.
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Alcoholes/administración & dosificación , Desinfectantes/administración & dosificación , Higiene de las Manos/organización & administración , Promoción de la Salud/organización & administración , Administración en Salud Pública/métodos , Adulto , Femenino , Adhesión a Directriz/estadística & datos numéricos , Experimentación Humana , Humanos , Masculino , Aceptación de la Atención de Salud , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
The aim of this study is to examine whether rapid polymerase chain reaction (PCR)-based screening is a cost-efficient tool to optimize pre-emptive antibiotic therapy of methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA, respectively) infections. A decision analytic cost model was developed, based on data from the peer-reviewed literature. Sensitivity analyses were undertaken to investigate the impact of variation in the MRSA rate, cost ratio of the cost of inappropriate antibiotic therapy to the cost of appropriate antibiotic therapy, PCR test cost, and total hospital costs per case. At a current MRSA rate of 24.5 % in Germany, PCR-guided treatment regimens are cost-efficient compared to empirical strategies. The costs of alternative treatment strategies differ, on average, up to 1,780
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Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana/economía , Pruebas de Sensibilidad Microbiana/métodos , Reacción en Cadena de la Polimerasa/economía , Reacción en Cadena de la Polimerasa/métodos , Infecciones Estafilocócicas/tratamiento farmacológico , Costos y Análisis de Costo/métodos , Infección Hospitalaria/microbiología , Alemania , Humanos , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genéticaRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a serious challenge for health care institutions, which is inherent in the combination of prevalence, transmission rates and costs. Furthermore, performing an MRSA screening requires information on the complex system of effectiveness, accuracy and costs of different screening methods. The purpose of this study was to give an overview of parameters with decisive significance for the burden of MRSA and the selection of a specific MRSA screening strategy. A systematic literature search for peer-reviewed health economic studies associated with MRSA was performed (from 1995 to the present). Eighty-seven different studies met all inclusion and exclusion criteria. Primary outcomes included the prevalence of MRSA, MRSA transmission rates, performance characteristics of MRSA screening methods, costs for pre-emptive isolation precautions and costs per MRSA case. The prevalence rates reported for all inpatients (1.2-5.3 %) as well as for inpatients with risk factors or patients in risk areas (3.85-20.6 %) vary greatly. The range of cross-transmission rates per day reported for patients with MRSA in isolation is 0.00081-0.009 and for carriers not in isolation is 0.00137-0.140, respectively. For polymerase chain reaction (PCR) methods, the mean sensitivity and specificity were 91.09 and 95.79 %, respectively. Culture methods show an average sensitivity of 89.01 % and an average specificity of 93.21 %. The turn-around time for PCR methods averages 15 h, while for the culture method, it can only be estimated as 48-72 h. This review filtered important parameters and cost drivers, and covered them with literature-based averages. These findings serve as an ideal evidence base for further health economic considerations of the cost-effectiveness of different MRSA screening methods.
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Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/economía , Infecciones Estafilocócicas/transmisión , Técnicas de Tipificación Bacteriana/normas , Costos y Análisis de Costo , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/economía , Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , Técnicas de Cultivo/métodos , Alemania/epidemiología , Humanos , Tamizaje Masivo/métodos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Prevalencia , Factores de Riesgo , Sensibilidad y Especificidad , Infecciones Estafilocócicas/microbiologíaRESUMEN
Urofacial syndrome (UFS) describes the combination of urological problems and an inverted facial expression upon attempts to smile. Seventeen independent familial cases from different ethnicities have been described so far. Some of these have been linked to chromosome 10q. Very recently, homozygous loss-of-function mutations affecting the gene HPSE2 were identified in nine cases. Here, we describe a consanguineous UFS family from Pakistan with three of six siblings affected. We establish linkage to the chromosome 10q critical region and identify two non-synonymous HPSE2 variants. In silico analysis and screening of controls defines c.631T>C (p.Y211H) as a novel benign SNP and c.1628A>T (p.N543I) as the disease-causing mutation. Our study exemplifies the challenges in proper clinical diagnosis of UFS and, thereby, supports the hypothesis of the disease being under diagnosed. By identifying the first HPSE2 missense mutation it also provides a starting point for studies aimed at functionally understanding the unusual combination of symptoms as characterizing UFS.
Asunto(s)
Cromosomas Humanos Par 10/genética , Glucuronidasa/genética , Mutación Missense , Enfermedades Urológicas/genética , Adolescente , Secuencia de Aminoácidos , Estudios de Casos y Controles , Niño , Análisis Mutacional de ADN , Facies , Femenino , Ligamiento Genético , Pruebas Genéticas , Genotipo , Humanos , Patrón de Herencia , Masculino , Datos de Secuencia Molecular , Linaje , Enfermedades Urológicas/diagnósticoRESUMEN
Recently, the HACCP (Hazard Analysis and Critical Control Points) concept was proposed as possible way to implement process-based hygiene concepts in clinical practice, but the extent to which this food safety concept can be transferred into the health care setting is unclear. We therefore discuss possible ways for a translation of the principles of the HACCP for health care settings. While a direct implementation of food processing concepts into health care is not very likely to be feasible and will probably not readily yield the intended results, the underlying principles of process-orientation, in-process safety control and hazard analysis based counter measures are transferable to clinical settings. In model projects the proposed concepts should be implemented, monitored, and evaluated under real world conditions.
RESUMEN
We developed a cryostat suitable for a laser scanning confocal microscope which allows for a short working distance and thus the usage of an objective with a high numerical aperture ensuring high collection efficiency. The in situ preparation of a thin layer of amorphous water is realized in a part of the cryostat, a Dewar vessel, which is put onto a custom-made, liquid-nitrogen immersed spin-coater. First tests on the setup are performed on a perylenemonoimide/polymethyl methacrylate model system using a standard oil objective and a dry objective at ambient temperature as well as a dry objective at liquid nitrogen temperature (77 K). Fluorescence resonance energy transfer (FRET) measurements on doubly labeled, freeze-quenched polyproline chains show the applicability of the new method on biomolecules. The alternating laser excitation (ALEX) is modified to a line-scanning process (slow ALEX) to optimize the sorting of the labeled molecules. Photophysics and photochemistry at liquid nitrogen temperature are investigated.
Asunto(s)
Transferencia Resonante de Energía de Fluorescencia/instrumentación , Microscopía Confocal/instrumentación , Fenómenos Ópticos , Temperatura , Nitrógeno/química , Péptidos/química , Procesos Fotoquímicos , Polimetil Metacrilato/químicaRESUMEN
BACKGROUND/AIMS: Mutations in the acid-labile subunit (ALS) gene (IGFALS) have been associated with circulating insulin-like growth factor I (IGF-I) deficiency and short stature. Whether severe pubertal delay is also part of the phenotype remains controversial due to the small number of cases reported. We report 2 children with a history of growth failure due to novel IGFALS mutations. METHODS: The growth hormone receptor gene (GHR) and IGFALS were analyzed by direct sequencing. Ternary complex formation was studied by size exclusion chromatography. RESULTS: Two boys of 13.3 and 10.6 years, with pubertal stages 2 and 1, had mild short stature (-3.2 and -2.8 SDS, respectively) and a biochemical profile suggestive of growth hormone resistance. No defects were identified in the GHR. Patient 1 was homozygous for the IGFALS missense mutation P73L. Patient 2 was a compound heterozygote for the missense mutation L134Q and a novel GGC to AG substitution at position 546-548 (546-548delGGCinsAG). The latter causes a frameshift and the appearance of a premature stop codon. Size exclusion chromatography showed no peaks corresponding to ternary and binary complexes in either patient. CONCLUSION: Screening of the IGFALS is important in children with short stature associated with low serum IGF-I, IGFBP-3 and ALS.
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Proteínas Portadoras/genética , Glicoproteínas/deficiencia , Glicoproteínas/genética , Trastornos del Crecimiento/genética , Adolescente , Niño , Consanguinidad , Mutación del Sistema de Lectura , Heterocigoto , Homocigoto , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Mutación MissenseRESUMEN
Methicillin resistance of Staphylococcus aureus strains (MRSA) has become a steadily growing cost factor for the German and international health system. Besides direct costs for diagnostics and therapy, indirect and intangible costs are a considerable part in the total expenses. Because of the massive increase of MRSA in medical centres as well as in the population and further worsening of forced rationalizing in the health care systems, the interest in the economic effects of this phenomenon has increased greatly during the last years. For managing MRSA and for effective cost containment, especially in hospitals, infection control measures have not only to prevent the further spread of MRSA but actively reduce the number of colonised patients. In the last years the efficiency of several infection control measures and their combination to prevent the spread of MRSA has been shown. However, these measures are linked to considerable direct costs in the first place. Nevertheless, an overall economic assessment of hygiene measures is only possible after a complete cost-benefit analysis, where costs are compared to effects achieved. Moreover, analyses that focus on effects for single institutions only are as inappropriate as purely monetary analyses or analyses that include the direct additional only. Despite of at first considerable expenditures, not only infection control measures but proactive strategies to reduce the total number of MRSA cases (accordingly of the "Search and Destroy" philosophy) are shown to be cost efficient, even in low prevalence situations, based on examples in literature. Hence, effective programmes to reduce MRSA are not only necessary from a medical and ethical focus but are also cost efficient in medium term for health care providers and the community.
Asunto(s)
Atención a la Salud/economía , Costos de la Atención en Salud/estadística & datos numéricos , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/economía , Infecciones Estafilocócicas/prevención & control , Alemania , HumanosRESUMEN
The juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease, MIM 204200), is an autosomal recessive lysosomal storage disease, which is characterized by ubiquitous accumulation of the lipopigment material ceroid-lipofuscin. It manifests with loss of vision in childhood due to retinal degeneration, followed by seizures and parkinsonism leading to premature death at around 30 years. Eighty-five percent of JNCL patients carry a disease-causing 1.02 kb deletion in the CLN3 gene on chromosome 16. Here we report on a large consanguineous Lebanese family with five affected siblings. Electron microscopy of lymphocytes revealed the presence of fingerprint profiles suggesting JNCL. However, disease progression, especially of mental and motor function was slower as expected for 'classic' JNCL. We thus confirmed the diagnosis by genetic testing and found a new c.597C>A transversion in exon 8, homozygous in all affected family members and not present in 200 alleles of normal controls. The mutation generates a premature termination codon (p.Y199X) truncating the CLN3 protein by 55%. In heterozygous state mutant mRNA transcripts are expressed at the same levels as the wild-type ones, suggesting the absence of nonsense mediated messenger decay. We discuss a potential residual catalytic function of the truncated protein as a cause for the mild phenotype.