A solute gradient in the tear meniscus I. A hypothesis to explain Marx's line

Marx's line is a line of mucosal staining behind the mucocutaneous junction. It can be demonstrated throughout life in all normal lids by staining with lissamine green and related dyes. Of all the body orifices, only the mucosae of the eye and mouth are directly exposed to the atmosphere. In this paper, we suggest that for the eye, this exposure leads to the formation of Marx's line. The tear meniscus thins progressively toward its apex, where it is pinned at the mucocutaneous junction of the lid. It also thins toward the black line, which segregates the meniscus from the tear film after the blink. We predict that, because of the geometry of the tear meniscus, evaporation generates a solute gradient across the meniscus profile in the anteroposterior plane, which peaks at the meniscus apices at the end of the interblink. One outcome would be to amplify the level of tear molarity at these sites so that they reach hyperosmolar proportions. Preliminary mathematical modeling suggests that dilution of this effect by advection and diffusion of solute away from the meniscus apex at the mucocutaneous junction will be restricted by spatial constraints, the presence of tear and surface mucins at this site, and limited fluid flow. We conclude that evaporative water loss from the tear meniscus may result in a physiological zone of hyperosmolar and related stresses to the occlusal conjunctiva, directly behind the mucocutaneous junction. We hypothesize that this stimulates a high epithelial cell turnover at this site, incomplete epithelial maturation, and a failure to express key molecules such as MUC 16 and galectin-3, which, with the tight junctions between surface epithelial cells, are necessary to seal the ocular surface and prevent penetration of dyes and other molecules into the epithelium. This is proposed as the basis for Marx's line. In Part II of this paper (also published in this issue of The Ocular Surface), we address additional pathophysiological consequences of this mechanism, affecting lid margins

A solute gradient in the tear meniscus II. implications for lid margin disease, including meibomian gland dysfunction

We have hypothesized previously that evaporation from the tears generates a solute gradient across the tear meniscus, which delivers hyperosmolar stress to the mucocutaneous junction (MCJ) of the lid margin. This is proposed as the basis for Marx's line, a line of staining with topically applied dyes that lies directly behind the MCJ. In this article, we consider the implications of this hypothesis for progressive damage to the lid margin as an age-related phenomenon, its amplification in dry eye states, and its possible role in the etiology of meibomian gland dysfunction (MGD). It is suggested that a hyperosmolar or related stimulus, acting behind the MCJ over a lifetime, promotes the anterior migration of the MCJ, which is a feature of the aging lid margin. This mechanism would be amplified in dry eye states, not only by reason of increased tear molarity at the meniscus apex but also by raising the concentration of inflammatory peptides at this site. This could explain the increased width and irregularity of Marx's line in dry eye. While the presence of stem cells at the lid margin may equip this region to respond to such stress, their depletion could be the basis of irreversible lid margin damage. It is further proposed, given the proximity of the MCJ to the meibomian gland orifices, that the solute gradient mechanism could play a role in the initiation of MGD by delivering hyperosmolar and inflammatory stresses to the terminal ducts and orifices of the glands. By the same token, the presence of a zone of increased epithelial permeability in this region may provide a back door route for the delivery of drugs in the treatment of MGD

A mass and solute balance model for tear volume & osmolarity in the normal and the dry eye

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye.\ud \ud The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity.\ud \ud Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable

Hepatic artery thrombosis after liver transplantation: Radiologic evaluation

Hepatic artery thrombosis after liver transplantation is a devastating event requiring emergency retransplantation in most patients. Early clinical signs are often nonspecific. Before duplex sonography (combined real-time and pulsed Doppler) capability was acquired in October 1984, 76% of all transplants in this institution referred for angiography with a clinical suspicion of hepatic artery thrombosis had patent arteries. In an effort to reduce the number of negative angiograms, CT, real-time sonography, and pulsed Doppler have been evaluated as screening examinations to determine which patients need angiography. Of 14 patients with focal inhomogeneity of the liver architecture detected by CT and/or real-time sonography, 12 (86%) had hepatic artery thrombosis, one had slow arterial flow with hepatic necrosis, and one had a biloma with a patent hepatic artery. In 29 patients undergoing duplex sonography of the hepatic artery, six (21%) had absence of a Doppler arterial pulse. All six had abnormal angiograms: Four had thrombosis, one had a significant stenosis, and one had slow flow with biopsy-proven ischemia. Of 23 patients with a Doppler pulse, two had hepatic artery thrombosis at surgery. However, real-time sonography demonstrated focal inhomogeneity in the liver in both cases. Our data demonstrate that pulsed Doppler of the hepatic artery combined with real-time sonography of the liver parenchyma currently is the optimal screening test for selecting patients who require hepatic angiography after liver transplantation. A diagnostic algorithm is provided

Left hepatic trisegmentectomy

Left hepatic trisegmentectomy was successfully performed upon four patients in whom the true left lobe of the liver and all, or part, of the anterior segment of the right lobe of the liver were removed in continuity. Three of the patients had carcinoma of the liver, and the fourth patient had a hemangioma and arteriovenous malformation. This procedure, which has not been described before, should allow subtotal hepatic resection to be performed upon some patients who have lesions that have been classified as inoperable, in the past

Opbrengstgericht werken op de PABO: een verkenning van de wenselijkheid en mogelijkheden om opbrengstgericht werken met behulp van een leerlingvolgsysteem in het pabo curriculum op te nemen

Opbrengstgericht werken (OGW) kan men typeren als een aanpak waarmee gestreefd wordt naar maximale leerprestaties van alle leerlingen. Meer opbrengstgerichte scholen blijken betere prestaties te boeken dan scholen die deze aanpak van OGW niet of nog minder in de praktijk brengen. In verband daarmee is het wenselijk dat aanstaande leraren basisonderwijs tijdens hun initiële opleiding ook gedegen worden voorbereid op zich de veranderende beroepspraktijk en zich de theorie en praktijk van OGW eigen te maken. OGW blijkt op veel pabo’s nog geen geïntegreerd onderdeel van het curriculum uit te make

Accuracy of computerized tomography in determining hepatic tumor size in patients receiving liver transplantation or resection

Computerized tomography (CT) of liver is used in oncologic practice for staging tumors, evaluating response to treatment, and screening patients for hepatic resection. Because of the impact of CT liver scan on major treatment decisions, it is important to assess its accuracy. Patients undergoing liver transplantation or resection provide a unique opportunity to test the accuracy of hepatic-imaging techniques by comparison of finding of preoperative CT scan with those at gross pathologic examination of resected specimens. Forty-one patients who had partial hepatic resection (34 patients) or liver transplantation (eight patients) for malignant (30 patients) or benign (11 patients) tumors were evaluable. Eight (47%) of 17 patients with primary malignant liver tumors, four (31%) of 13 patients with metastatic liver tumors, and two (20%) of 10 patients with benign liver tumors had tumor nodules in resected specimens that were not apparent on preoperative CT studies. These nodules varied in size from 0.1 to 1.6 cm. While 11 of 14 of these nodules were 1.0 cm. These results suggest that conventional CT alone may be insufficient to accurately determine the presence or absence of liver metastases, extent of liver involvement, or response of hepatic metastases to treatment