Largest recent impact craters on Mars: Orbital imaging and surface seismic co-investigation.

Two >130-meter-diameter impact craters formed on Mars during the later half of 2021. These are the two largest fresh impact craters discovered by the Mars Reconnaissance Orbiter since operations started 16 years ago. The impacts created two of the largest seismic events (magnitudes greater than 4) recorded by InSight during its 3-year mission. The combination of orbital imagery and seismic ground motion enables the investigation of subsurface and atmospheric energy partitioning of the impact process on a planet with a thin atmosphere and the first direct test of martian deep-interior seismic models with known event distances. The impact at 35°N excavated blocks of water ice, which is the lowest latitude at which ice has been directly observed on Mars.

Surface waves and crustal structure on Mars.

We detected surface waves from two meteorite impacts on Mars. By measuring group velocity dispersion along the impact-lander path, we obtained a direct constraint on crustal structure away from the InSight lander. The crust north of the equatorial dichotomy had a shear wave velocity of approximately 3.2 kilometers per second in the 5- to 30-kilometer depth range, with little depth variation. This implies a higher crustal density than inferred beneath the lander, suggesting either compositional differences or reduced porosity in the volcanic areas traversed by the surface waves. The lower velocities and the crustal layering observed beneath the landing site down to a 10-kilometer depth are not a global feature. Structural variations revealed by surface waves hold implications for models of the formation and thickness of the martian crust.

Potential Pitfalls in the Analysis and Structural Interpretation of Seismic Data from the Mars InSight Mission.

The Seismic Experiment for Interior Structure (SEIS) of the InSight mission to Mars, has been providing direct information on Martian interior structure and dynamics of that planet since it landed. Compared to seismic recordings on Earth, ground motion measurements acquired by SEIS on Mars are made under dramatically different ambient noise conditions, but include idiosyncratic signals that arise from coupling between different InSight sensors and spacecraft components. This work is to synthesize what is known about these signal types, illustrate how they can manifest in waveforms and noise correlations, and present pitfalls in structural interpretations based on standard seismic analysis methods. We show that glitches, a type of prominent transient signal, can produce artifacts in ambient noise correlations. Sustained signals that vary in frequency, such as lander modes which are affected by variations in temperature and wind conditions over the course of the Martian Sol, can also contaminate ambient noise results. Therefore, both types of signals have the potential to bias interpretation in terms of subsurface layering. We illustrate that signal processing in the presence of identified nonseismic signals must be informed by an understanding of the underlying physical processes in order for high fidelity waveforms of ground motion to be extracted. While the origins of most idiosyncratic signals are well understood, the 2.4 Hz resonance remains debated and the literature does not contain an explanation of its fine spectral structure. Even though the selection of idiosyncratic signal types discussed in this paper may not be exhaustive, we provide guidance on best practices for enhancing the robustness of structural interpretations.

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users.

Anti-hiperglycemic effect of Quassia amara (Simaroubaceae) in normal and diabetic rats / Efeito anti-hiperglicêmico de Quassia amara (Simaroubaceae) em ratos normais e diabéticos

The anti-hyperglycemic effect of wood powder of Quassia amara (QA) was evaluated in normal and in alloxan diabetes-induced rats. After a 12 h fast and glycemic check, the animals were orally given 0.9% of saline (control group), metformin (500 mg/kg) or QA (200 mg/kg) and, 30 minutes later, they received an oral glucose dose (1g/kg). The blood glucose level was measured after 30, 60, 90 and 120 minutes. From the oral glucose dose, QA showed anti-hyperglycemic effects, similar to metformin, only in the diabetic animals (p<0.01) when compared to the control group. Although the anti-hyperglycemic mechanism of action of QA was not investigated, a mechanism similar to metformin can be suggested, since both presented similar results for the conditions tested, that is, normal and diabetic rats. It is believed that the use of QA in diabetics could help to control the blood glucose levels and be useful as an alternative therapy.

O efeito anti-hiperglicemiante do pó do lenho de Quassia amara (QA) foi avaliado em ratos normais e diabéticos aloxana induzidos. Após jejum de 12 horas e verificação da glicemia, os animais receberam administração oral de salina 0.9% (grupo controle), metformina (500 mg/kg) ou QA (200 mg/kg) e 30 minutos depois carga oral de glicose (1g/kg). A glicemia foi medida nos próximos 30, 60, 90 e 120 minutos. A partir da carga oral de glicose, a QA mostrou efeito anti-hiperglicemiante, similar a metformina, somente nos animais diabéticos (p<0.01) quando comparados ao grupo controle. Embora o mecanismo de ação anti-hiperglicemiante da QA não tenha sido investigado, podemos sugerir um mecanismo semelhante à metformina, visto que ambos apresentaram resultados similares nas duas condições testadas, ou seja, animais normais e diabéticos. Acredita-se que o uso de QA, em diabéticos, possa auxiliar no controle da glicemia e servir como terapia alternativa.

Gluconeogenesis and ketogenesis in perfused liver of rats submitted to short-term insulin-induced hypoglycaemia.

Gluconeogenesis and ketogenesis of in situ rat perfused liver submitted to short-term insulin-induced hypoglycaemia (IIH) were investigated. For this purpose, 24-h fasted rats that received intraperitoneal (ip) regular insulin (1.0 U kg(-1)) or saline were compared. The studies were performed 30 min after insulin (IIH group) or saline (COG group) injection. For gluconeogenesis studies, livers from the IIH and COG groups were perfused with increasing concentrations (from basal blood concentrations until saturating concentration) of glycerol, L-lactate (Lac) or pyruvate (Pyr). Livers of the IIH group showed maintained efficiency to produce glucose from glycerol and higher efficiency to produce glucose from Lac and Pyr. In agreement with these results the oral administration of glycerol (100 mg kg(-1)), Lac (100 mg kg(-1)), Pyr (100 mg kg(-1)) or glycerol (100 mg kg(-1)) + Lac (100 mg kg(-1)) + Pyr (100 mg kg(-1)) promoted glycaemia recovery. It can be inferred that the increased portal availability of Lac, Pyr and glycerol could help glycaemia recovery by a mechanism mediated, partly at least, by a maintained (glycerol) or increased (Lac and Pyr) hepatic efficiency to produce glucose. Moreover, in spite of the fact that insulin inhibits ketogenesis, the capacity of the liver to produce ketone bodies from octanoate during IIH was maintained.

Blood amino acids concentration during insulin induced hypoglycemia in rats: the role of alanine and glutamine in glucose recovery.

Our purpose was to determine the blood amino acid concentration during insulin induced hypoglycemia (IIH) and examine if the administration of alanine or glutamine could help glycemia recovery in fasted rats. IIH was obtained by an intraperitoneal injection of regular insulin (1.0 U/kg). The blood levels of the majority of amino acids, including alanine and glutamine were decreased (P < 0.05) during IIH and this change correlates well with the duration than the intensity of hypoglycemia. On the other hand, the oral and intraperitoneal administration of alanine (100 mg/kg) or glutamine (100 mg/kg) accelerates glucose recovery. This effect was partly at least consequence of the increased capacity of the livers from IIH group to produce glucose from alanine and glutamine. It was concluded that the blood amino acids availability during IIH, particularly alanine and glutamine, play a pivotal role in recovery from hypoglycemia.

Acute effects of isolated and combined L-alanine and L-glutamine on hepatic gluconeogenesis, ureagenesis and glycaemic recovery in experimental short-term insulin induced hypoglycaemia.

The acute effects of isolated and combined L-alanine (L-Ala) and L-glutamine (L-Gln) on liver gluconeogenesis, ureagenesis and glycaemic recovery during short-term insulin-induced hypoglycaemia (IIH) were investigated. For this purpose, 24-h fasted rats that received intraperitoneal injection of regular insulin (1.0 U/Kg) were investigated. The control group (COG group) were represented by rats which received saline. The studies were performed 30 min after insulin (IIH group) or saline (COG group) injection. Livers from IIH and COG groups were perfused with basal or saturating levels of L-Ala, L-Gln or L-Gln + L-Ala (L-G + L-A). The production of glucose, urea, L-lactate and pyruvate in livers from IIH and COG group were markedly increased (p < 0.001) when perfused with saturating levels of L-Ala, L-Gln or L-G + L-A compared with basal levels of the same substrates. In addition, livers from IIH rats showed greater ability in producing glucose and urea from saturating levels of L-Ala compared with L-Gln or L-G + L-A. In agreement with these results, the oral administration of L-Ala (100 mg/kg) promoted better glycaemic recovery than L-Gln (100 mg/kg) or the combination of L-G (50 mg/kg) + L-A (50 mg/kg). It can be concluded that L-Ala, but not L-Gln or L-G + L-A could help glycaemic recovery by a mechanism mediated, partly at least, by the increased gluconeogenic and ureagenic efficiency of L-Ala.

Lifting frontal apoyado en malla de polipropileno / Brow lift supported on polypropylen mesh

La región frontorbitaria tiene una especial significación en el contexto del envejecimiento facial. La literatura cuenta con numerosa bibliografía que trata sobre este problema. Se considera como una unidad diagnóstico-terapéutica en los últimos tiempos y la evolución de la cirugía hace que se vaya hacia soluciones cada vez más fisiológicas y mínimamente invasivas. Nuestro trabajo queremos que sea un paso más en esa dirección. Sobre una muestra de 25 pacientes en los que se trató la región frontorbitaraia con diferentes procedimientos, y que además mostraban un descenso de la altura de las cejas, se presenta una técnica de suspensión frontorbitaria con mínima incisión, apoyada en una malla de polipropileno anclada en el músculo frontal y galea en el extremo inferior y en el periostio y la galea en su extremo superior en el plano supraperióstico y sin resección cutánea. Se emplea un sistema de medición de resultados basado en puntos del esqueleto facial. Los resultados han sido satisfactorios subjetiva y objetivamente, y comparables a los de otras técnicas más complejas y de mayor coste económico. Las complicaciones desarrolladas han sido leves y pasajeras. Se valora porqué se decidió utilizar la malla de polipropileno, así como porqué se eligió un gramaje concreto. También se analizan las características que aportan el material y su uso en esta técnica como comportamiento ante la infección, tolerancia tisular, retracción cicatricial y adhesividad. Asímismo se justifica el plano de disección y colocación elegido, y se valora el sistema de medición para el control objetivo de los resultados. La aportación de este trabajo consiste en desarrollar una alternativa dentro de las técnicas mínimamente invasivas para le reposición de la región frontorbitaria, sin resección de piel y con buenos resultados en la corrección de las arrugas frontales, comparables a los de otras técnicas de mayor complejidad y elevado coste económico (AU)

The fronto-orbital region is of particular significance in the context of facial ageing. There is a considerable amount of research on the nature of this problem. This area has recently come to be considered as a therapeutic- diagnostic unit and surgical developments mean that focus is switching more towards less invasive physiological solutions. Our study aims to take another step in this direction. ;;Taking a sample of 25 patients, all of them undergoing different procedures on the fronto-orbital region and with a lowering of the eyebrows, a suspension technique was introduced with minimum incisions supported by a polypropylene mesh attached to the frontal muscle and galea in the inferior extreme and to the periosteum and galea in the superior extreme in the supra-periosteum plane and without skin removal. A measuring system based on points of the facial skeleton was used. ;;The results were subjectively and objectively satisfactory compared to those from more complicated and expensive techniques. Complications were of a slight and temporary nature. ;;This section carries out an assessment of the reasons for selecting a polypropylene mesh and specific grammage. In addition, the properties of the material are analysed and its use in this context of preventing infection, tissue tolerance, scar reduction and adhesiveness. Justification of the site of dissection and the choice of positioning, and an assessment of the course of medication given in order to produce a set of controlled and objective results, will also be carried out. ;;The aim of this work is to develop an alternative within minimally invasive techniques for the restructuring of the fronto-orbital region without skin removal and with good results in the correction of facial wrinkles compared to other more complicated and expensive techniques (AU)

Análisis de las hospitalizaciones de pacientes ingresados en la unidad de cirugía sin ingreso (UCSI) / Analysis of unplanned admissions in an outpatient department

INTRODUCCIÓN: El análisis de los resultados es fundamental para corregir los fallos y posibles errores de un procedimiento. Dado que la última fase del alta de los pacientes son realizados mayoritariamente por personal de enfermería, nosotros filtramos aquí los datos derivados del fracaso de la Unidad ( UCSI), al realizar un seguimiento de los pacientes que en vez de pasar a su domicilio, tuvieron destino en hospitalización. MATERIAL Y MÉTODOS: Se han estudiado los primeros 1950 ingresos realizados en la Unidad de Cirugía sin ingreso (UCSI) que pertenecían a los Servicios de Cirugía con 273 (14’00%), Oftalmología 1.304 (66’87%), Traumatología con 317 (16’25%) y Urología con 56 (2’87%). Los ingresos se agrupan además por Servicios y médico responsable; los pacientes con hospitalización como destino se agrupan además por causas de hospitalización como de errores de selección, causas anestésicas, causas técnicas, causas postoperatorias y otras. RESULTADOS: Los pacientes que pasaron a hospitalización fueron 88 en total (4’51%) pertenecieron 8 a Cirugía, 46 a Oftalmología, 9 a traumatología, ninguno a Urología y 26 a Anestesiología, Con respecto a los grupos de causas: de los 88 pacientes 5 tuvieron que pasar a hospitalización por errores en la selección de los pacientes (5’68%), 9 por problemas de tipo anestésico (10’22%), 43 por circunstancias técnicas intraoperatorias (48’86%), 17 por su evolución postoperatoria propiamente en UCSI (19’31%) y 14 por otras causas (15’90%). También se ha analizado cada médico responsable, lo cual ha llevado a descubrir en algún caso vicios de procedimiento por parte de alguno de éllos. CONCLUSIONES: Aunque los porcentajes se hallan dentro de los rangos descritos en la literatura, el análisis de los fracasos es el mejor criterio para realizar un control de calidad permitiendo corregir los defectos y vicios de funcionamiento (AU)

INTRODUCTION: The analysis of results is essential for the correction of errors or possible mistakes in any process. The last phase before the patients are discharged from hospital is undertaken by nursing staff. Bearing this in mind, we present the data obtained from the "failed ambulatory procedures" of the Day Surgery Unit (DSU). It concerns those patients that were hospitalised instead of being sent home. MATERIAL AND METHODS: The present study dealt with the first 1950 admissions to the Day Surgery Unit (DSU) from which 273 (14%) were of the Surgery department, 1304 (66.87%) of the Ophthalmology department, 317 (16.25%) of the Trauma department and 56 (2.87%) of the Urology department. The admissions analysed are grouped in the different departments and the doctors in charge. Furthermore, those patients that were hospitalised were grouped according to the reasons for that: selection errors; anaesthetic reasons; technical reasons; postoperative reasons and others. RESULTS: Of the total of patients, 88 (4.51%) were hospitalised. Of these, 8 belonged to Surgery, 46 to Ophthalmology, 9 to Trauma, none to Urology and 26 to Anaesthesia, which represents 2.93% of the total in Surgery, 3.52% in Ophthalmology, 2.83% in Trauma, and 1.74% in Anaesthesia. Depending on the causes, of the (..) (AU)

Cirugía ambulatoria en tumores cervicales / Ambulatory surgery for cervical tumours

TIPO DE ESTUDIO: Descriptivo PACIENTES Y MÉTODO: Se presentan 10casos de Tumoraciones Cervicales: 3 nódulos tiroideos, 2 quistes tiroglosos,2 adenomas parotídeos,1 Tumor submaxilar, 1 litiasis/abceso submaxilary 1 quiste branquial tratadas en régimen de Cirugía Mayor Ambulatoria. Los criterios de selección varían poco con respecto a los convencionales, así como el tratamiento quirúrgico, ya que solo en las hemitiroidectomías se trataba de evitar la extensión del cuello; y la vigilancia postoperatoria en el Hospital era igual a la que se aplica a cualquier otra patología. Se ha realizado un seguimiento postoperatorio personalizado, en el que el paciente tenía acceso directo a su equipo quirúrgico durante las primeras 24horas postoperatorias. RESULTADOS: Los resultados han sido buenos, ya que no se han producido complicaciones. Se hace una valoración de la actitud con respecto a las complicaciones mas graves que se podían haber producido. Conclusiones: Se concluye que este grupo de patología nodular tiroidea se puede incluir entre las entidades de CMA (AU)

KIND OF STUDY: Descriptive. SETTING: A Public General Hospital. MATERIAL AND METHODS: We present 10cases of Cervical Tumours: 3 thyroid nodules, 2thyroglossal cysts, 2 parotid adenomas, 1 submaxillary tumour, 1 submaxillary lithiasis/abscess and 1 branchial cyst. All these tumours were treated in a Day Surgery Unit (DSU). Both the selection criteria and the surgical treatment hardly differed from that used in conventional procedures except in hemithyroidectomies where we tried to avoid extension of the neck. Postoperative observation during hospital stay was the same as that applied to any other pathology. Personalized postoperative monitoring was carried out allowing the patient to have direct access to his surgical team during the 24 hours following the operation. RESULTS: The results are good as there have been no complications. We evaluated the attitude towards possible complications which mayarise. CONCLUSION: We concluded that this group of nodular thyroid pathology may be included among Ambulatory procedures (AU)

Analysis of marginal donor parameters in liver transplantation for primary biliary cirrhosis.

The shortage in cadaveric donor livers is pushing the transplant centers to expand the pool by using "marginal" donors. Primary biliary cirrhosis (PBC) remains an important indication for transplantation. We conducted a retrospective analysis of prospectively collected data in a well-defined group of patients with PBC where 301 consecutive donor-PBC recipient pairs transplanted were analyzed to identify donor and operative factors influencing recipient outcome. Mean follow-up was 56 months. The 1-, 3- and 5-year actuarial patient and graft survival was 93.97%, 90.64%, and 81.75%, and 85.49%, 82.57%, and 75.21%, respectively. Factors showing influence in decreased total patient survival were recipient old age (P = 0.003) and low recipient albumin (P = 0.01). However, the only variables showing an association with decreased patient survival within 90 days are old donor age (P = 0.002) and high donor body weight (P = 0.03) or high body mass index (BMI) (P = 0.055). Cold ischaemic time (CIT) of 18 hours showed statistical significance in patient survival (P = 0.025). Obesity did have a significant adverse impact on survival compared with normal or overweight donors (BMI < 30), decreasing survival by 50% at 5 years. In conclusion, this study of several factors considered "marginal" for transplantation in a recipient population with predictable liver disease (PBC), donor BMI and age were shown to be associated with decreased graft and patient survival.

Granular parakeratosis

This is a report of a 60 year-old black female patient presenting with pruritic brownish crusted plaques on both axillae of one month evolution. Histopathology revealed findings characteristic of axillary granular parakeratosis. This entity was first described by Northcutt et al in 1991. Since then, involvement of other intertriginous areas have also been reported. A review of the literature was performed and the term granular parakeratosis is suggested to emphasize its pathognomonic histopathologic features

Liver transplantation in patients over sixty years of age.

BACKGROUND: Although some centers have reported very good patient and graft survival in liver allograft recipients, reports from both North America (United Network of Organ Sharing) and Europe (European Liver Transplantation Registry) have failed to confirm this. AIM: We have reviewed our experience of liver transplantation in older recipients and compared their clinical outcome to a younger group. METHODS: Retrospective analyses were conducted on 875 consecutive adult patients undergoing liver transplantation for chronic liver disease, between 1990 and 1999. Group I consisted of patients under 60 years of age (n=701; 80.2%) and group II of patients over 60 years (n=174; 19.8%). RESULTS: The proportion of older patients transplanted increased from 10.15% between 1990-1991 to 20.85% (1997-1999). Actuarial graft survival at 1, 3, and 5 years was 78%, 74%, and 69% and 78%, 73%, and 66% for groups I and II, respectively (P=0.49). The overall actuarial patient survival tended to be better in the younger group (1-, 3-, and 5-year survival of 83%, 79%, and 76% for group I and 81%, 75%, and 69% for group II (P=0.07). Crude mortality probability shows a stable trend until 45 years, a gradual increase in mortality between 45 and 60 years, and then the risk of death is accelerated. The same analysis shows the risk of death is between 1.5 and 2 times greater in Child C patients; this is greater in patients aged more than 66 years. CONCLUSION: There is no statistically significant difference in patient or graft survival in patients aged over 60 compared to younger recipients. However, when age is assessed as a continuous variable, an adverse effect of older age is seen on outcome and this effect is more marked in sicker patients.

Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center.

Orthotopic liver transplantation (OLT) is an effective treatment for patients with advanced primary biliary cirrhosis (PBC). We have conducted a retrospective analysis of 400 consecutive patients transplanted for PBC between 1983 and 1999. Mean follow-up was 56 months. The proportion of patients grafted for PBC fell progressively, from 35% in 1990 (n = 80) to 21% in 1999 (n = 111); comparison of patients grafted in the 2 decades showed that the median age increased from 53 to 56 years and the median serum bilirubin at transplantation fell from 270 micromol/L to 132 micromol/L. The overall actuarial patient and graft survival at 1, 5, and 10 years is 83%, 78%, and 67% and 82%, 75%, and 61%, respectively. The net gain in 5-year survival compared with predicted survival in the absence of transplantation fell from 37% (range, 82%-90%) to 16% (range, 91%-99%). Multiple organ failure (16.1%) and sepsis (9.6%) were the major causes of early deaths (<6 months). Recurrent PBC, diagnosed on allograft histology, was found in 68 (17%) patients, at a mean time of 36 months. We were unable to identify any pretransplantation donor or recipient factor, which identified those patients at risk of recurrence, although recurrence was much earlier and more frequently seen in patients receiving tacrolimus (P =.04). PBC remains a good indication for liver transplantation, with excellent survival rates. The age at transplantation increased although patients tended to be grafted earlier. Survival rates have increased although there is a reduction in the survival benefit. Recurrence may be common, but does not seem to affect medium-term graft survival.

Recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation.

BACKGROUND: Non-alcoholic steatohepatitis was coined in 1980 to describe pathological and clinical features of non-alcoholic disease associated with pathological features, commonly seen in alcoholic-liver disease itself. It is now a well-recognised cause of end-stage liver disease and a rare cause of orthotopic liver transplantation. A small number of cases with recurrent non-alcoholic steatohepatitis following liver transplantation have been reported, however de novo non-alcoholic steatohepatitis in the liver allograft is not well recognised. AIMS/RESULTS: We report four cases of non-alcoholic steatohepatitis following orthotopic liver transplantation describing the factors related with the pathology. The recurrence of fatty infiltration occurred within 21 months and transition from mild steatosis to non-alcoholic steatohepatitis and early fibrosis was observed within 60 months post transplant in all four patients. All four cases had association with one or multiples risk factors (obesity, type 2 diabetes and/or hyperlipidemia). CONCLUSIONS: Management of this risk factors may play a therapeutic role in the prevention of recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation.

Chronic rejection of the liver: the role of immunosuppression.

Liver transplantation is now widely recognised as an effective treatment option for patients with advanced liver disease. Many units now achieve greater than 85% survival at 1 year, with the majority of patients having a high quality of life. The maintenance of a high quality of life requires careful clinical management to ensure that the continued maintenance of excellent liver graft function is not achieved at the expense of immunosuppressive drug complications or morbidity. Acute liver rejection will occur in between 30 to 45% of patients, although with modern immunosuppressive protocols, usually combining one of the calcineurin agents, either cyclosporin or tacrolimus, with both azathioprine and corticosteroids (prednisolone) ensures that relatively few grafts are lost from severe acute rejection. While the incidence and severity of acute rejection may be one factor in raising the risk of chronic rejection, it may not be the principal one in many patients. It is important to recognise that the frequency of rejection also varies with the primary underlying liver disease, with patients with hepatitis B or alcoholic liver disease having relatively low rejection rates, compared with patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), which range between 20 to 70%. Chronic rejection will account for some 5% of grafts lost in the first 3 to 5 years. Indeed, there is some evidence that the incidence of chronic rejection is actually declining over the past few years. While the reason for this apparent decline is uncertain, and it could relate to better immunosuppression management, or more likely to the growing recognition that chronic graft dysfunction may be due to recurrent liver disease, such as autoimmune hepatitis, PBC, PSC, or recurrent hepatitis C. The differentiation of recurrent primary liver disease from chronic rejection can prove to be very difficult in clinical practice. Thus, the clinician must carefully monitor liver and graft function, evaluate any biochemical changes, and try to reach a clear diagnosis before considering any modification of immunosuppressive schedules.

Retinal findings and characteristics in AIDS patients with systemic Mycobacterium avium-intracellulare complex and toxoplasmic encephalitis.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the incidence and characteristics of retinal and choroidal manifestations of toxoplasmosis and/or Mycobacterium avium-intracellulare complex (MAC) in patients with acquired immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: The authors analyzed their prospectively collected data and found 120 patients with new retinal lesions (group A) that were diagnosed 3 months or longer following the diagnosis of MAC and/or toxoplasmic encephalitis. The authors also performed a point prevalence study of retinal/choroidal findings in 25 consecutive AIDS patients (group B) without known eye disease who had been recently treated for toxoplasmic encephalitis and/or disseminated MAC infections. In addition, the characteristics of retinochoroidal toxoplasmosis scars in 5 AIDS patients were studied and compared with the characteristics of scars in 18 immunocompetent patients. RESULTS: In this study the incidence of ocular manifestations of MAC was zero (95% confidence interval [CI] 0.0% to 3.8%). Two of 25 patients (8%) (95% CI 1% to 26%) in group A and 2 of 11 patients (18.1%) (95% CI 3.3% to 51.8%) in group B had toxoplasmic retinochoroiditis. CONCLUSION: In AIDS patients, ocular manifestations of toxoplasmosis are more common than ocular MAC. In addition, when compared with immunocompetent patients, AIDS patients tend to have retinochoroidal scars with less retinal pigment epithelium hyperplasia (1.8+ vs 3+) (P = .03).

Polymerase chain reaction detection of cytomegalovirus and human immunodeficiency virus-1 in the retina of patients with acquired immune deficiency syndrome with and without cotton-wool spots.

PURPOSE: The authors determine the association, if any, between detection of human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) nucleic acids and retinal lesions in patients with acquired immune deficiency syndrome. METHODS: Postmortem eyes were examined with a dissecting microscope and light microscopy. Retinal cotton-wool spots (CWS) were removed using a clean touch punch biopsy technique. Equivalent amounts of retinal tissue from the posterior pole of the retina not affected by CWS and from the retinal periphery also were studied. Polymerase chain reaction (PCR) detection of retinal cellular DNA (GA3PD gene), human CMV DNA (major immediate early gene), and HIV (gag gene) was performed using ethidium bromide and liquid hybridization detection. RESULTS: Ninety percent of CWS were positive for CMV DNA versus 22% of peripheral retinal biopsies (P < 0.025). Liquid hybridization showed similar results. Analysis of lesions in which results of both tests were positive (ethidium and liquid hybridization) versus lesions in which results of either test were negative also showed a strong association between CWS and CMV, but not HIV nucleic acids (P < 0.02). Studies of HIV showed no association between retinal CWS lesions and HIV nucleic acid; with liquid hybridization HIV, RNA was detected equally at low levels in all areas. CONCLUSION: There is a statistically significant association between the presence of human CMV nucleic acids and retinal CWS detected by PCR. There is a low level presence of HIV in the retinal tissue studied that is only detectable using liquid hybridization techniques and is not associated with a particular area or lesions in the retina; this may represent detection of HIV in blood. The presence of CMV in areas of retinal CWS may have implications for their pathogenesis, but further study is necessary because other explanations are possible.

Intravitreous and plasma concentrations of ganciclovir and foscarnet after intravenous therapy in patients with AIDS and cytomegalovirus retinitis.

This study evaluated intravitreous and plasma ganciclovir and foscarnet concentrations after intravenous administration in AIDS patients with cytomegalovirus (CMV) retinitis and retinal detachment. Undiluted vitreous samples were prospectively obtained from 60 eyes (52 patients) at the time of pars plana vitrectomy. Thirty-three plasma samples (from 27 patients in the initial group of 52) were obtained simultaneously during surgery on 33 eyes. High-pressure liquid chromatography showed the mean vitreous ganciclovir concentrations in patients on induction and maintenance therapy were, respectively, 4.74 +/- 1.49 microM (n = 24) and 3.29 +/- 1.84 microM (n = 30; P = .005). Simultaneous plasma ganciclovir concentrations were less than the vitreous concentrations in 78% of the patients. The mean intravitreous foscarnet concentrations in patients receiving induction dosages were 189 +/- 177 microM (n = 5) versus 163 +/- 167 microM (n = 4; P > .20) for those receiving maintenance therapy. The foscarnet vitreous plasma concentration ratio averaged 1.43. Current drugs and doses for CMV retinitis result in borderline or progressively subtherapeutic concentrations.