Locally advanced breast implant-associated anaplastic large-cell lymphoma: a combined medical-surgical approach.

OBJECTIVE: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin's T-cell lymphoma that develops around breast implants. CASE PRESENTATION: This report illustrates the case of a patient affected by a locally advanced BIA-ALCL which infiltrated the thoracic wall (stage T4N0M0) following implant-based reconstruction after left mastectomy. Given the initial inoperability due to the patient's poor general condition, the treatment plan provided for a primary cycle of systemic neoadjuvant immunotherapy/chemotherapy, surgical removal of the mass, and subsequent systemic chemotherapy/immunotherapy. This resulted in complete remission - the patient remained disease-free even over a year later - without the need for adjuvant radiotherapy. CONCLUSIONS: Our real-life case shows how the existing guidelines can be successfully adapted as part of an individualized approach to advanced and/or difficult cases.

Guías basadas en la evidencia para el uso de traqueostomía en el paciente crítico / Evidence-based guides in tracheostomy use in critical patients

OBJETIVOS: Proporcionar guías de traqueostomía para el paciente crítico, basadas en la evidencia científica disponible, y facilitar la identificación de áreas en las cuales se requieren mayores estudios. MÉTODOS: Un grupo de trabajo formado con representantes de 10 países pertenecientes a la Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva y a la Latin American Critical Care Trial Investigators Network (LACCTIN) desarrollaron estas recomendaciones basadas en el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS: El grupo identificó 23 preguntas relevantes entre las 87 preguntas planteadas inicialmente. En la búsqueda inicial de la literatura se identificaron 333 estudios, de los cuales se escogieron un total de 226. El equipo de trabajo generó un total de 19 recomendaciones: 10 positivas (1B=3, 2C=3, 2D=4) y 9 negativas (1B=8, 2C=1). En 6 ocasiones no se pudieron establecer recomendaciones. CONCLUSIÓN: La traqueostomía percutánea se asocia a menor riesgo de infecciones en comparación con la traqueostomía quirúrgica. La traqueostomía precoz solo parece reducir la duración de la ventilación mecánica pero no la incidencia de neumonía, la duración de la estancia hospitalaria o la mortalidad a largo plazo. La evidencia no apoya el uso de broncoscopia de forma rutinaria ni el uso de máscara laríngea durante el procedimiento. Finalmente, el entrenamiento adecuado previo es tanto o más importante que la técnica utilizada para disminuir las complicaciones

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used

Evidence-based guides in tracheostomy use in critical patients

Objetivos: Proporcionar guías de traqueostomía para el paciente crítico, basadas en la evidencia científica disponible, y facilitar la identificación de áreas en las cuales se requieren mayores estudios. Métodos: Un grupo de trabajo formado con representantes de 10 países pertenecientes a la Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva y a la Latin American Critical Care Trial Investigators Network(LACCTIN) desarrollaron estas recomendaciones basadas en el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: El grupo identificó 23 preguntas relevantes entre las 87 preguntas planteadas inicialmente. En la búsqueda inicial de la literatura se identificaron 333 estudios, de los cuales se escogieron un total de 226. El equipo de trabajo generó un total de 19 recomendaciones: 10 positivas (1B = 3, 2C = 3, 2D = 4) y 9 negativas (1B = 8, 2C = 1). En 6 ocasiones no se pudieron establecer recomendaciones. Conclusión: La traqueostomía percutánea se asocia a menor riesgo de infecciones en comparación con la traqueostomía quirúrgica. La traqueostomía precoz solo parece reducir la duración de la ventilación mecánica pero no la incidencia de neumonía, la duración de la estancia hospitalaria o la mortalidad a largo plazo. La evidencia no apoya el uso de broncoscopia de forma rutinaria ni el uso de máscara laríngea durante el procedimiento. Finalmente, el entrenamiento adecuado previo es tanto o más importante que la técnica utilizada para disminuir las complicaciones.(AU)

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used.(AU)

Evidence-based guides in tracheostomy use in critical patients. / Guías basadas en la evidencia para el uso de traqueostomía en el paciente crítico.

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used.

Sistema robótico guía para la inserción de tornillos en cirugía de fijación de columna / Robotic Guide System for Insertion of Screws in Spinal Fixation Surgery

El presente artículo muestra el diseño y operación de un primer prototipo de robot para la guía en la inserción de tornillos en cirugía de fijación de columna. Este tipo de cirugía, realizada normalmente de forma manual, puede producir muchas lesiones debido a errores humanos al momento de introducir los tornillos en las vértebras del paciente. Para evitar dichos errores se puede utilizar la tomografía computarizada, pero los resultados son mucho mejores si un robot asistente proporciona al cirujano el camino para la inserción del tornillo, según la imagen del tomógrafo. Este artículo muestra como utilizando un robot comercial de bajo costo se puede implementar un sistema que provee una solución funcional a este problema. Se implementó un software que permite definir la posición inicial y final del tornillo a ser introducido, sobre la imagen Dicom del paciente. Con esta información el sistema mueve el robot el cual posee un anillo que guiará al cirujano en la inserción final. Los resultados muestran un sistema bastante preciso ofreciendo al cirujano un camino seguro de inserción.

This article presents the design and operation of the first prototype of a robot, designed to guide the insertion of screws in spinal fixation surgery. This type of surgery, usually done manually, could cause many injuries due to human error at the moment of inserting the screws into the patient’s vertebrae. Computed tomography can be used to avoid such errors, but the results are much better if a robot assists and indicates the surgeon the path for the insertion of the screw, according to the image scanner. This article shows how using a commercial low-cost robot can be implemented in a system that provides a practical solution to this problem. A software that allows you to define the start and the end positions of the screw to be introduced on the Dicom image of the patient, was implemented. With this information the system moves the robot which has a ring that will guide the surgeon in the final insertion. The results show a fairly accurate system, giving the surgeon a safe path of insertion.

Self-assembled titanium calcium oxide nanopatterns as versatile reactive nanomasks for dry etching lithographic transfer with high selectivity.

We report the simple preparation of ultra-thin self-assembled nanoperforated titanium calcium oxide films and their use as reactive nanomasks for selective dry etching of silicon. This novel reactive nanomask is composed of TiO(2) in which up to 50% of Ti was replaced by Ca (Ca(x)Ti(1-x)O(2-x)). The system was prepared by evaporation induced self-assembly of dip-coated solution of CaCl(2), TiCl(4) and poly(butadiene-block-ethylene oxide) followed by 5 min of thermal treatment at 500 °C in air. The mask exhibits enhanced selectivity by forming a CaF(2) protective layer in the presence of a chemically reactive fluorinated plasma. In particular it is demonstrated that ordered nano-arrays of dense Si pillars, or deep cylindrical wells, with high aspect ratio i.e. lateral dimensions as small as 20 nm and height up to 200 nm, can be formed. Both wells and pillars were formed by tuning the morphology and the homogeneity of the deposited mask. The mask preparation is extremely fast and simple, low-cost and easily scalable. Its combination with reactive ion etching constitutes one of the first examples of what can be achieved when sol-gel chemistry is coupled with top-down technologies. The resulting Si nanopatterns and nanostructures are of high interest for applications in many fields of nanotechnology including electronics and optics. This work extends and diversifies the toolbox of nanofabrication methods.

All-silica nanofluidic devices for DNA-analysis fabricated by imprint of sol-gel silica with silicon stamp.

We present a simple and cheap method for fabrication of silica nanofluidic devices for single-molecule studies. By imprinting sol-gel materials with a multi-level stamp comprising micro- and nanofeatures, channels of different depth are produced in a single process step. Calcination of the imprinted hybrid sol-gel material produces purely inorganic silica, which has very low autofluorescence and can be fusion bonded to a glass lid. Compared to top-down processing of fused silica or silicon substrates, imprint of sol-gel silica enables fabrication of high-quality nanofluidic devices without expensive high-vacuum lithography and etching techniques. The applicability of the fabricated device for single-molecule studies is demonstrated by measuring the extension of DNA molecules of different lengths confined in the nanochannels.

Valor diagnóstico y pronóstico de la determinación de tripsinógeno-2 urinario en pacientes con pancreatitis aguda / Usefulness of determining urinary trypsinogen-2 in diagnosis and prognosis of patients with acute pancreatitis

Fundamento. Estudiar el papel del tripsinógeno-2 urinarioen el diagnóstico y pronóstico inicial de pacientescon pancreatitis aguda (PA) así como su relación con laestancia media hospitalaria y la mortalidad.Método. Se incluyeron 42 pacientes diagnosticados dePA a los que se realizó hematimetría, bioquímica sanguínea,amilasuria y tripsinógeno-2 urinario. Se establecióun punto de corte de 50 μg/L y una segunda dilución a2.000 μg/L. Otras variables incluidas fueron etiología, estanciamedia hospitalaria, traslado a UCI y fallecimiento.Resultados. De los 42 pacientes, 29 (69%) eran hombresy 13 (31%) mujeres; edad media 61 años. La etiologíamás frecuente era la biliar, seguida del alcohol. Estanciamedia: 8,38 días. Traslado a UCI en 4 (9,5%) pacientes.Dos de los pacientes trasladados a UCI y otro que norequirió traslado fallecieron (7,14%). La amilasa séricafue elevada en 33 (78,57%) pacientes y la lipasa en36 (85,71%). El tripsinógeno urinario fue positivo en34 pacientes (80,95%). Se evidenció asociación entretripsinógeno-2 urinario y edad (p=0,016; r=0,893), glucemia(p=0,005, r=0,901), amilasa plasmática (p=0,029;r=0,852), lipasa (p=0,022; r=0,809) e hipoxemia (p=0,001;r=0,962). En cuanto a la estancia media, se observóasociación estadística con edad (p=0,046; r=0,784) yacidosis metabólica (p=0,016; r=0,839). La mortalidadse asoció a hipocalcemia (p=0,008; r=0,899) y acidosismetabólica (p=0,032; r=0,814).Conclusión. La determinación del tripsinógeno-2 urinarioen pacientes con PA es un test útil y rápido. Lospacientes mayores de 65 años, con hipoxemia, acidosismetabólica e hipocalcemia tienen tendencia a presentaruna estancia media hospitalaria prolongada y mayormortalidad(AU)

Background. To study the role of urinary trypsinogen-2in diagnosing and early prognosis of patients with acutepancreatitis (AP) and the relationship to length of hospitalstay and mortality.Methods. Forty-two patients were included in the study.In all cases, blood cell count, serum chemistry, urineamylase and urine trypsinogen-2 were measured. Acut-off of 50 μg/L was established and, when positive, asecond dilution was made (2000 μg/L). Other variablesincluded were etiology, mean length of hospital stay,transfer to an ICU and death.Results. Out of the 42 patients, 29 (69%) were men and13 (31%) women. Average age was 61 years. The most frequentcause was biliary, followed by alcohol. Mean hospitalstay was 8.38 days. Transferred to an ICU: 4 (9.5%)patients. Two of them and a third, who had not beentransferred, died (7.14%). High serum amylase was foundin 33 (78.57%) patients and high lipase in 36 (85.71%).Urinary trypsinogen-2 was positive in 34 patients(80.95%). Statistical association between urinary trypsinogen-2 and age (p=0.016; r=0.893), glucose (p=0.005;r=0.901), serum amylase (p=0.029; r=0.852), lipase(p=0.022; r=0.809) and hypoxemia (p=0.001; r=0.962) wasfound. Regarding hospital stay, there was statistical associationwith age (p=0.046; r=0.784) and metabolic acidosis(p=0.016; r=0.839). With respect to mortality therewas statistical association with hypocalcemia (p=0.008;r=0.899) and metabolic acidosis (p=0.032; r=0.814).Conclusion. Testing urinary trypsiongen-2 in patientswith AP is rapid and useful. Patients over the age of 65with hypoxia, metabolic acidosis and hypocalcemiatend to present a prolonged average hospital stay andhigher mortality(AU)

[Usefulness of determining urinary trypsinogen-2 in diagnosis and prognosis of patients with acute pancreatitis]. / Valor diagnóstico y pronóstico de la determinación de tripsinógeno-2 urinario en pacientes con pancreatitis aguda.

BACKGROUND: To study the role of urinary trypsinogen-2 in diagnosing and early prognosis of patients with acute pancreatitis (AP) and the relationship to length of hospital stay and mortality. METHODS: Forty-two patients were included in the study. In all cases, blood cell count, serum chemistry, urine amylase and urine trypsinogen-2 were measured. A cut-off of 50 microg/L was established and, when positive, a second dilution was made (2000 microg/L). Other variables included were etiology, mean length of hospital stay, transfer to an ICU and death. RESULTS: Out of the 42 patients, 29 (69%) were men and 13 (31%) women. Average age was 61 years. The most frequent cause was biliary, followed by alcohol. Mean hospital stay was 8.38 days. Transferred to an ICU: 4 (9.5%) patients. Two of them and a third, who had not been transferred, died (7.14%). High serum amylase was found in 33 (78.57%) patients and high lipase in 36 (85.71%). Urinary trypsinogen-2 was positive in 34 patients (80.95%). Statistical association between urinary trypsinogen-2 and age (p=0.016; r=0.893), glucose (p=0.005; r=0.901), serum amylase (p=0.029; r=0.852), lipase (p=0.022; r=0.809) and hypoxemia (p=0.001; r=0.962) was found. Regarding hospital stay, there was statistical association with age (p=0.046; r=0.784) and metabolic acidosis (p=0.016; r=0.839). With respect to mortality there was statistical association with hypocalcemia (p=0.008; r=0.899) and metabolic acidosis (p=0.032; r=0.814). CONCLUSION: Testing urinary trypsinogen-2 in patients with AP is rapid and useful. Patients over the age of 65 with hypoxia, metabolic acidosis and hypocalcemia tend to present a prolonged average hospital stay and higher mortality.

Purification of poly-ubiquitinated proteins by S5a-affinity chromatography.

Poly-ubiquitination, the post-translational covalent conjugation of isopeptide-linked chains of ubiquitin to other target proteins, is the central signal for proteolytic degradation by the 26S proteasome complex. The S5a subunit of the 26S proteasome binds poly-ubiquitin chains containing four or more ubiquitins. We have used an immobilised glutathione-S-transferase (GST)-S5a fusion protein to purify poly-ubiquitinated proteins from mammalian tissues, with the intention of expanding the repertoire of known substrates of the ubiquitin pathway. A complex mixture of poly-ubiquitinated proteins was successfully purified from normal pig brain extract following induction of in vitro ubiquitination. Western blots of two-dimensional gels of this mixture showed at least two diagonal series of ubiquitin-positive spots. Individual spots in each series were separated by approximately 9 kDa suggesting that they represent poly-ubiquitinated proteins with increasing numbers of ubiquitins in the chains. S5a-binding proteins purified from ubiquitination-induced human placental extracts, resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis and visualised by Coomassie staining, contained a single major species with an apparent denatured molecular mass of approximately 60 kDa. Edman degradation identified this protein as hHR23B, a human homologue of the Saccharomyces cerevisiae DNA repair protein Rad23p. In this case hHR23B is not ubiquitinated but instead contains an intrinsic ubiquitin-like domain at its N-terminus, through which it interacts with S5a (Hiyama, H., et al., J Biol. Chem. 1999, 274, 28,019-28,025).

The ubiquitin protein catabolic disorders.

The ubiquitin-proteasome system of intracellular proteolysis is essential for cell viability. We propose the concept that neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as other conditions including some types of cancer, collectively represent a raft of 'ubiquitin protein catabolic disorders' in which altered function of the ubiquitin-proteasome system can cause or directly contribute to disease pathogenesis. Genetic abnormalities within the ubiquitin pathway, either in ubiquitin-ligase (E3) enzymes or in deubiquitinating enzymes, cause disease because of problems associated with substrate recognition or supply of free ubiquitin, respectively. In some cases, mutations in protein substrates of the ubiquitin-proteasome system may directly contribute to disease progression because of inefficient substrate recognition. Mutations in transcripts for the ubiquitin protein itself (as a result of 'molecular misreading') also affect ubiquitin-dependent proteolysis with catastrophic consequences. This has been shown in Alzheimer's disease and could apply to other age-associated neurodegenerative conditions. Within the nervous system, accumulation of unwanted proteins as a result of defective ubiquitin-dependent proteolysis may contribute to aggregation events, which underlie the pathogenesis of several major human neurodegenerative diseases.

[Utilization of health care system by patients with chronic pain who apply for disability pensions. A registry study]. / Forbrug af sundhedssystemet hos kroniske smertepatienter der søger førtidspension. En registerundersøgelse.

INTRODUCTION: Patients with chronic pain may be awarded a disability pension if their working capacity is reduced as a result of an illness. Patients with chronic pain very often consult several specialists in order to obtain proof of their illness. The aim of this study was to investigate how an application for disability pension affected the utilization of health care services by patients with chronic pain. METHOD: Patients with chronic pain who applied for a disability pension in 1989 and 1990 were entered. The study period was divided into three: the year preceding the submission of the application for a disability pension, the time from submission of the application to the making of the decision, and the year following the decision of the health authorities. The patients were divided into four subgroups according to whether the disability pension was awarded or rejected, and whether the patients accepted or appealed the decision. The total costs of care in the primary sector were calculated on the number of and charges for visits to GPs and the total costs of hospital care were calculated on the number of bed days, visits to outpatients clinics, operations, and investigations. RESULTS: Patients with chronic pain had a significantly lower health care utilisation after the case has been closed. Those who did not get a disability pension and those who were not satisfied with the level of the disability pension, continued their utilisation of health care after the decision. The mean health care used by patients who appealed the level of the disability pension was three times higher than that used by patients who accepted the level of the disability pension. CONCLUSION: The study indicates that lack of or insufficient economic compensation from the social system in patients with chronic pain may contribute to inexpedient behaviour leading to increased costs to the health care sector.

Inhibition of the ubiquitin-proteasome system in Alzheimer's disease.

Alzheimer's disease is the most common cause of dementia in the elderly. Although several genetic defects have been identified in patients with a family history of this disease, the majority of cases involve individuals with no known genetic predisposition. A mutant form of ubiquitin, termed Ub(+1), has been selectively observed in the brains of Alzheimer's patients, including those with nonfamilial Alzheimer's disease, but it has been unclear why Ub(+1) expression should be deleterious. Here we show that Ub(+1) is an efficient substrate for polyubiquitination in vitro and in transfected human cells. The resulting polyubiquitin chains are refractory to disassembly by deubiquitinating enzymes and potently inhibit the degradation of a polyubiquitinated substrate by purified 26S proteasomes. Thus, expression of Ub(+1) in aging brain could result in dominant inhibition of the Ub-proteasome system, leading to neuropathologic consequences.

Economic evaluation of programmes aiming at eradicating infectious diseases.

The subject of this article is to discuss the global and regional economic aspects of programmes for eradicating infectious diseases. The perspective on the issue is that scarce health care resources should be employed in the best possible way. The task is then to examine what the best possible use might be. A starting point is by asking the relevant policy questions attached to eradications: Is there a suitable technique, what are the costs, and what are the benefits? Of particular importance is the opportunity cost of using resources on eradication when other health care problems may require more urgent donation of resources. The paper attempts to set up a generic model for economic evaluation of eradication programmes. But, as there are many different treatment strategies varying from one country to another, such a generic model may need modifications to suit a particular strategy. However, the paper is contextual and should only be viewed as guidance for those wishing to conduct an economic analysis of eradication programmes, or as a initiative to create discussion among health care decision makers.

The Danish approach to standards for economic evaluation methodologies.

Standards for economic evaluation have now been proposed in several countries. The background for this article is a report commissioned in 1994 by the Danish health authorities (the National Board of Health and the Danish Ministry of Health) on the state of the art of economic evaluation: are the methods ready to be used for systematic decision-making in the Danish healthcare sector? The themes of this article are the attitude towards economic evaluation of medical technologies and healthcare services in Denmark, the areas for application and the desirability and feasibility of a standard set of methods for conducting economic evaluations. In addition, the current state of methodologies in economic evaluation is briefly outlined. On the background of a roundtable discussion of interested parties, the Danish health authorities have decided to introduce economic evaluation of new pharmaceutical products, on a voluntary basis for 2 to 3 years, when application has been made for public reimbursement.

Overexpression of bcl-2 alters usage of mutational hot spots in germinal center B cells.

Bcl-2 is an anti-apoptotic gene important in B cell development. In order to study how apoptosis regulates somatic hypermutation and selection of B cell clones in the germinal center, we examined the antibody response to phosphorylcholine (PC) in transgenic mice overexpressing bcl-2 in the B cell compartment. The anti-PC antibody response is dominated by the S107V1 variable region heavy chain gene. We, therefore, analyzed S107V1-encoded heavy chains from germinal center cells. The proportion of germinal center sequences that were mutated, and the frequency of mutations did not differ significantly between the two groups of mice. No significant differences were found in the clustering of replacement mutations in the complementarity determining regions (CDRs) and in replacement to silent (R:S) mutation ratios. A significant difference between bcl-2 transgenic mice and controls, however, was found in the targeting of mutations to oligonucleotide motifs presumed to be mutational "hot spots." While non-transgenic mice displayed the expected clustering of mutations in hot spots, mutations from bcl-2 transgenic mice lacked this pattern. This observation suggests that the mechanism for somatic hypermutation includes two distinct functions, a non-specific mutational apparatus and a mechanism to target mutation to hot spots, and that in certain circumstances these functions may be uncoupled.

High serum IgA concentrations in patients with diabetes mellitus: agewise distribution and relation to chronic complications.

In this study we investigated the agewise distributions of serum IgA concentrations in 1251 type 1 and 2224 type 2 diabetic patients, and the association between serum IgA concentration and diabetic complications (retinopathy, neuropathy, nephropathy, macroangiopathy, and hypertension). The IgA concentrations of all groups of diabetic patients were significantly higher than those of the corresponding subgroups of 943 control subjects, except for type 1 patients >60 years of age. High IgA concentrations were found in 23.1% of the whole diabetic group. The prevalence of high IgA was significantly greater in males than in females among type 1 patients (24.4% vs 18%). In conclusion, an increase in circulating IgA concentrations is a generalized phenomenon among diabetic patients; IgA concentrations above the reference range are more common among male than female diabetics; and diabetic complications are associated with a significant increase in serum IgA concentration.

The role of economic appraisal in Denmark.

The numbers of economic appraisals conducted have been increasing during the last ten years in Denmark. This article involves 17 economic appraisals on specific health issues. Most of the studies use the cost-effectiveness approach. Cost appraising has only been conducted in five of the studies, three use the cost-benefit approach, and only one uses the cost-utility approach. Most of the studies have been directed at the policy level and only five have been directed at the clinical decision making level. The success of the individual economic appraisals is being assessed by looking at their ability to change behaviour among the decision makers according to the results obtained and by looking at their ability to enter the decision making process. However, as this article stresses, economic appraisals have also been used to introduce the economic appraisal approach as a way of thinking, as a road to efficiency, within the health services. This has led to the incorporation of economic appraisals into committee work at the National decision making level, the issuing of guidelines to local health authorities including efficiency, and to some acceptance of the efficiency term among health professionals.