Medical management: Its accomplishments in Crohn's disease and indications for surgery

While the etiology of Crohn's disease remains unknown, the optimal treatment of patients with this complaint must include integrated medical and surgical management.Crohn's disease is, in practice, not a single disorder but comprises a wide variety of disorders masquerading under the one name, so that each patient requires careful individual evaluation, including a review of previous resections and a clear definition of the site and extent of macroscopic disease. Any anemia and fluid or electrolyte depletion must be detected and rectified. Local complications such as stricture, abscess, or enterocutaneous fistula must be identified, and secondary complications such as renal stones, gallstones, or peptic ulcer considered. Symptomatic relief of diarrhea with codeine phosphate, Lomotil^®, or loperamide may be appropriate. In symptomatic patients with nonobstructing Crohn's disease, specific therapy using sulphasalazine, metronidazole, corticosteroids, or immunosuppressive therapy may play a useful shortterm role. In a few patients, dietary manipulation and enteral or parenteral feeding may be of value. Several controlled trials have shown that specific medical treatment is not of any benefit either for patients with quiescent disease or for asymptomatic patients after resection of their lesions. Crohn's disease complicated by the occurrence of a stricture, an intraabdominal abscess, or an enterocutaneous fistula lies essentially within the province of the surgeon. Many patients with Crohn's colitis respond initially to specific medical treatment, but relapses are common, so that resection is appropriate in those patients with chronic ill health; there is a negligible mortality in experienced hands. The risk of recurrent disease should not delay surgical treatment, which can restore the chronically ill patient to good health, often for a considerable time. Furthermore, recurrent disease is commonly localized to the site of previous resection; if symptoms persist, a further resection can be undertaken with minimal morbidity.

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Resumen Aunque la etiología de la enfermedad de Crohn permanece desconocida, el tratamiento óptimo de los pacientes afectados por esta entidad debe incluír manejo tanto médico como quirurgico.La enfermedad de Crohn en realidad no es una alteración Única, sino más bien una variedad de alteraciones enmascaradas bajo una denominación, en tal forma que cada paciente requiere cuidadosa valoración individual incluyendo la revisión de resecciones quirÚrgicas previas y la definición de la ubicación y extensión de la enfermedad macroscópica; la anemia y la depleción de líquidos y electrolitos deben ser corregidas. Complicaciones localizadas, tales como estrecheces, abscesos, o fístulas enterocutáneas deben ser identificadas, y las complicaciones secundarias tales como cálculos renales o biliares, o ulceración péptica, deben ser tenidas en cuenta. El tratamiento sintomático de la diarrea con fosfato de codeína, Lomotil^®, o loperamida debe ser apropiado. En los pacientes sintomáticos con enfermedad de Crohn no obstructiva, la terapia específica con sulfasalazina, metronidazol, corticosteroides, o medicación inmunosupresiva puede jugar un papel Útil por tiempos limitados. En algunos casos, la manipulación dietética enteral o parenteral puede ser de utilidad. Algunos ensayos clínicos controlados han demostrado que el tratamiento médico específico no aporta beneficio a pacientes con enfermedad latente ni a pacientes sintomáticos una vez que les han sido resecadas sus lesiones macroscópicas.La enfermedad de Crohn con complicaciones como estrecheces, abscesos abdominales, o fístulas enterocutáneas es hoy del dominio del cirujano.Muchos pacientes con colitis de Crohn responden inicialmente al tratamiento médico pero la recidiva es lo comÚn y por ello la resección resulta apropiada para los casos de enfermedad crónica; la mortalidad es casi nula en manos experimentadas. El riesgo de recurrencia de la enfermedad no debe demorar el tratamiento quirÚrgico, el cual es capaz de restaurar un buen estado de salud en el paciente con padecimiento crónico. Además, la recurrencia comunmente afecta a segmentos intestinales cortos y se localiza en el lugar de anastomosis previas; si los síntomas persisten, debe emprenderse la resección adicional, la cual con mínima morbilidad, restablece rápidamente un buen estado de salud.

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Résumé Alors mÊme que l'édologie de la maladie de Crohn reste inconnue le traitement de l'affection relève de la médecine et de la chirurgie.La maladie de Crohn ne se manifeste pas de manière univoque mais se présente sous de multiples aspects si bien que chaque malade requiert une appréciation précise de son affection en définissant rigoureusement la localisation et l'extension des lésions et les résections qui ont déjà été pratiquées. Toute anémie ou déplétion hydroélectrolytique doit Être décelée et corrigée. Les complications locales telles que sténose, abcès, fistule entéro-cutanée doivent Être reconnues ainsi que les complications secondaires tels que calculs rénaux, calculs biliaires, ulcère peptique. Le traitement symptomatique de la diarrhée par la codéine, le Lomotil^® ou le loperamide peut Être indiqué chez les malades qui accusent des troubles mais ne présentent pas d'obstruction intestinale; un traitement spécifique comportant sulphasalazine, métronidazole, cortico-stéroides, agents immuno-suppresseurs peut jouer un rÔle utile à court terme. Chez quelques malades, la diététique et l'alimentation par voie entérale ou parentérale sont à envisager. Plusieurs essais contrÔlés ont montré que le traitement médical spécifique ne procure aucune amélioration chez les malades dont la maladie est en phase de quiescence ou chez les opérés qui ne présentent pas de troubles après résection des lésions.La maladie de Crohn compliquée de sténose, d'abcès intraabdominal, de fistule entéro-cutanée relève essentiellement de la chirurgie.De nombreuses lésions coliques répondent d'abord favorablement au traitement médical spécifique mais les récidives sont si fréquentes que la résection est indiquée chez ces malades en état de mal chronique d'autant que la mortalité est faible entre les mains de chirurgiens expérimentés. Il convient de devancer la récidive pour que le malade récupère un bon état de santé. En outre, lorsque la récidive se manifeste au niveau du site d'une résection antérieure, il convient, si les troubles persistent, de procéder à une nouvelle résection en raison de la faible morbidité opératoire.

     

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.     

The implementation of a knowledge-based pathology Hypertext under HyperCard

A knowledge-based Hypertext of Pathology integrating videodisc-based images and computer-generated graphics with the textual cognitive information of an undergraduate pathology curriculum has been developed. The system described in this paper was implemented under HyperCard⁰⁰ during 1988 and 1989. Three earlier versions of the system that were developed on different platforms are contrasted with the present system. Strengths, weaknesses, and future extensions of the system are enumerated. The conceptual basis and organizational principles of the knowledge base are also briefly discussed.     

Effects of muscimol inactivation of the cerebellar nuclei on precision grip

A single monkey was trained to perform a grasp, lift, and hold task in which a stationary hand- held object was sometimes subjected to brief, predictable force-pulse perturbations. The displacement, grip, and lifting forces were measured as well the three-dimensional forces and torques to quantify specific motor deficits after reversible inactivation of the cerebellar nuclei. A prior single-cell recording study in the same monkey provided the stereotaxic coordinates used to guide intranuclear injections of muscimol. In total, 34 penetrations were performed at 28 different loci throughout the cerebellar nuclei. On each penetration, two 1.0-microl injections of 5 microg/microl muscimol, were made 1.0 mm apart either within the nuclei or in the white matter just lateral or posterior to the dentate nucleus. Injections in the region corresponding to the anterior interpositus nucleus produced pronounced dynamic tremor and dysmetric movements of the ipsilateral arm when the animal performed unrestrained reaching and grasping movements. In contrast, no relatively short-latency (15-20 min.) deficits were observed after injection in the dentate nucleus, although some effects were observed after several hours. When tested in a primate chair with the forearm supported and restrained at the wrist and elbow, the monkey performed the lift and hold task without tremor or dysmetria. However, with the restraint removed, the forces and torques applied to the manipulandum were poorly controlled and erratic. The monkey's arm was ataxic and a 5-Hz intention tremor was clearly visible. In addition, the animal was generally unable to compensate for the predictable perturbations and the anticipatory grip force increases were absent. However, overall the results suggest that reversible cerebellar nuclear inactivation with muscimol has little effect on isolated distal movements of the wrist and fingers.     

Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.     

Amyloid beta-peptide(1-42) contributes to the oxidative stress and neurodegeneration found in Alzheimer disease brain

Oxidative stress is extensive in Alzheimer disease (AD) brain. Amyloid beta-peptide (1-42) has been shown to induce oxidative stress and neurotoxicity in vitro and in vivo. Genetic mutations that result in increased production of Abeta1-42 from amyloid precursor protein are associated with an early onset and accelerated pathology of AD. Consequently, Abeta1-42 has been proposed to play a central role in the pathogenesis of AD as a mediator of oxidative stress. In this review, we discuss the role of Abeta1-42 in the lipid peroxidation and protein oxidation evident in AD brain and the implications of such oxidative stress for the function of various proteins that we have identified as specifically oxidized in AD brain compared to control, using proteomics methods. Additionally, we discuss the critical role of methionine 35 in the oxidative stress and neurotoxic properties exhibited by Abeta1-42.     

Thrombus of the ascending aorta: a rare cause of myocardial infarction.

We present two cases of a thrombus in the ascending aorta causing an acute myocardial infarction (AMI) and review the 10 other cases previously reported in the literature. This life-threatening condition appears to be more common in female smokers in their fifth decade. Suspicion should be raised in individuals at low risk for atherosclerotic disease with coronary angiographic findings not in keeping with the clinical presentation. The diagnosis may be obtained by transesophageal echocardiography, and we generally recommend surgical thrombectomy.