Experiences of GP trainees in undertaking telephone consultations: a mixed-methods study.

Background: Primary care telephone consultations are increasingly used for patient triage, reviews, and providing clinical information. They are also a key postgraduate training component yet little is known about GP trainees' preparation for, or experiences and perceptions of, them.

Aim: To understand the experiences, perceptions, and training of GP trainees in conducting telephone consultations.

Lymphatic function is impaired following irradiation of a single lymph node.

Introduction: Lymph nodes are often the target of radiotherapy procedures. Unfortunately, the impact of nodal irradiation on lymphatic function is uncertain. In this study, our aim was to quantify the impact of lymph node irradiation on lymph flow.

Potential for intranasal drug delivery to alter cerebrospinal fluid outflow via the nasal turbinate lymphatics.

Background: Cerebrospinal fluid absorption (CSF) at the cribriform plate is mediated by direct extracranial connections to the lymphatic system. Given the accessibility of these pharmacologically responsive vessels we hypothesized that the rate of CSF outflow can be modulated via the intranasal delivery of drugs known to affect lymphatic contractile activity.

Findings: Fluid was infused into the lateral ventricle of anesthetized sheep and inflow rate and CSF pressure measured during intranasal administration of pharmacological agents.

Pre- and post-shunting observations in adult sheep with kaolin-induced hydrocephalus.

Background: The objective of this study was to examine host-shunt interactions in sheep with kaolin-induced hydrocephalus.

Methods: Forty-two sheep (29-40 kg) were utilized for this study. In 20 animals, various kaolin doses were injected into the cisterna magna including 10 and 50 mg/kg as well as 2-4 ml of a 25% kaolin suspension.

A MATHEMATICAL ANALYSIS OF PHYSIOLOGICAL AND MOLECULAR MECHANISMS THAT MODULATE PRESSURE GRADIENTS AND FACILITATE VENTRICULAR EXPANSION IN HYDROCEPHALUS.

Perhaps the greatest paradox in the hydrocephalus field is the failure of researchers to consistently measure transmantle pressure gradients (ventricle to subarachnoid space) in either human or animal models of the communicating form of the disorder. Without such a gradient, conceptualization of how ventricular distention occurs is difficult. Based on evidence from both a mathematical model [35] and experiments in skin [51], we observed that the intraventricular injection of anti-β integrin antibodies in rat brains results in a reduction of periventricular pressures to values below those monitored in the ventricles.

A model to measure lymphatic drainage from the eye.

Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and recently described ciliary body lymphatics.

Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy.

Introduction: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, post-surgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous lymph node transplantation has the potential to reduce or prevent edema development.

Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus.

Background: We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance).

Experimental assessment of autologous lymph node transplantation as treatment of postsurgical lymphedema.

Background: The authors' objective was to test whether the transplantation of an autologous lymph node into a nodal excision site in sheep would restore lymphatic transport function and reduce the magnitude of postsurgical lymphedema.

Methods: As a measure of lymph transport, iodine-125 human serum albumin was injected into prenodal vessels at 8 and 12 weeks after surgery, and plasma levels of the protein were used to calculate the transport rate of the tracer to blood (percent injected per hour). Edema was quantified from the circumferential measurement of the hind limbs.

Identification of lymphatics in the ciliary body of the human eye: a novel "uveolymphatic" outflow pathway.

Impaired aqueous humor flow from the eye may lead to elevated intraocular pressure and glaucoma. Drainage of aqueous fluid from the eye occurs through established routes that include conventional outflow via the trabecular meshwork, and an unconventional or uveoscleral outflow pathway involving the ciliary body. Based on the assumption that the eye lacks a lymphatic circulation, the possible role of lymphatics in the less well defined uveoscleral pathway has been largely ignored.

Intraventricular injection of antibodies to beta1-integrins generates pressure gradients in the brain favoring hydrocephalus development in rats.

In some tissues, the injection of antibodies to the beta(1)-integrins leads to a reduction in interstitial fluid pressure, indicating an active role for the extracellular matrix in tissue pressure regulation. If perturbations of the matrix occur in the periventricular area of the brain, a comparable lowering of interstitial pressures may induce transparenchymal pressure gradients favoring ventricular expansion. To examine this concept, we measured periventricular (parenchymal) and ventricular pressures with a servo-null micropipette system (2-microm tip) in adult Wistar rats before and after anti-integrin antibodies or IgG/IgM isotype controls were injected into a lateral ventricle.

Lymphedema development and lymphatic function following lymph node excision in sheep.

Background: Our objective was to develop an animal model of postsurgical lymphedema that would permit quantitation of edema and lymphatic function after the removal of a single popliteal lymph node in sheep.

Methods: As a measure of lymph transport, (125)I-human serum albumin was injected into prenodal vessels at 8, 12 and 16 weeks after nodal excision, and plasma levels of the protein tracer were used to calculate the transport rate of the tracer to blood (percent injected per hour). Edema was quantified from the circumferential measurement of the hind limbs.

Communicating hydrocephalus in adult rats with kaolin obstruction of the basal cisterns or the cortical subarachnoid space.

Communicating hydrocephalus (CH) occurs frequently, but clinically-relevant animal models amenable to diagnostic imaging and cerebrospinal fluid shunting are not available. In order to develop and characterize models of subarachnoid space (SAS) obstruction at the basal cisterns (BC) or cerebral convexities (CX), 25% kaolin was injected in adult female Sprague-Dawley rats following halothane anesthesia; intact- or saline-injected animals served as controls. For BC animals (n=28 hydrocephalics, n=20 controls), an anterior approach to the C1-clivus interval was employed and 30 microl of kaolin or saline was injected.

Properties of the lymphatic cerebrospinal fluid transport system in the rat: impact of elevated intracranial pressure.

Previous studies suggested that a major portion of cerebrospinal fluid (CSF) is absorbed by extracranial lymphatics located in the olfactory turbinates. The objective of this study was to determine the impact of elevated intracranial pressure (ICP) on downstream cervical lymphatic pressures in the rat. Pressures were measured in the deep cervical lymph nodes using a servo-null micropressure system.

Possible role of the cavernous sinus veins in cerebrospinal fluid absorption.

The purpose of this investigation was to enhance our understanding of cerebrospinal fluid (CSF) absorption pathways. To achieve this, Microfil (a coloured silastic material) was infused into the subarachnoid space (cisterna magna) of sheep post mortem, and the relevant tissues examined macroscopically and microscopically. The Microfil was taken up by an extensive network of extracranial lymphatic vessels in the olfactory turbinates.

Lymphangiogenesis following obstruction of large postnodal lymphatics in sheep.

We examined the impact of lymph flow obstruction in large post-nodal lymphatic vessels in sheep. A silk ligature was placed 2 cm downstream from the prescapular or popliteal lymph node and tightened to interrupt flow. At 6, 12 and 16 weeks after lymph flow blockage, a network of small interconnecting lymphatics (approximately 10-40 microm in diameter) could be observed in the vicinity of the ligature.

Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats.

A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport, 125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats.

What we don't (but should) know about hydrocephalus.

In an effort to identify critical gaps in the prevailing knowledge of hydrocephalus, the authors formulated 10 key questions. 1) How do we define hydrocephalus? 2) How is cerebrosinal fluid (CSF) absorbed normally and what are the causes of CSF malabsorption in hydrocephalus? 3) Why do the ventricles dilate in communicating hydrocephalus? 4) What happens to the structure and function of the brain when it is compressed and stretched by the expanding ventricles? 5) What is the role of cerebrovenous pressure in hydrocephalus? 6) What causes normal-pressure hydrocephalus? 7) What causes low-pressure hydrocephalus? 8) What is the pathophysiology of slit ventricle syndrome? 9) What is the pathophysiological basis for neurological impairment in hydrocephalus, and to what extent is it reversible? 10) How is the brain of a child with hydrocephalus different from that of a young or elderly adult? Rigorous answers to these questions should lead to more effective and reliable treatments for this disorder.

Development of cerebrospinal fluid absorption sites in the pig and rat: connections between the subarachnoid space and lymphatic vessels in the olfactory turbinates.

The textbook view that cerebrospinal fluid (CSF) absorption occurs mainly through the arachnoid granulations and villi is being challenged by quantitative and qualitative studies that support a major role for the lymphatic circulation in CSF transport. There are many potential sites at which lymphatics may gain access to CSF but the primary pathway involves the movement of CSF through the cribriform plate foramina in association with the olfactory nerves. Lymphatics encircle the nerve trunks on the extracranial surface of the cribriform plate and absorb CSF.

Integration of the subarachnoid space and lymphatics: is it time to embrace a new concept of cerebrospinal fluid absorption?

In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system.

Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species.

BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport.

The importance of lymphatics in cerebrospinal fluid transport.

Despite the fact that the central nervous system parenchyma does not contain lymphatics, extracranial lymphatic vessels play a very important role in volumetric cerebrospinal fluid (CSF) transport. The most important extracranial location at which lymphatics gain access to CSF is in the nasal submucosa after CSF convects through the cribriform plate. At relatively low intracranial pressures (ICPs), the majority of cranial CSF absorption occurs through this pathway.

Lymphatic vessels gain access to cerebrospinal fluid through unique association with olfactory nerves.

Background: Physiological studies suggest that a major portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. Especially important is CSF transport through the cribriform plate in association with the olfactory nerves. This study examined the anatomical connections that link the CSF and extracranial lymphatics at the base of the brain.

Long-term in vivo biomechanical properties and biocompatibility of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) nerve conduits.

Artificial grafts are promising alternatives to nerve grafts for peripheral nerve repair because they obviate the complications and disadvantages associated with autografting such as donor site morbidity and limited tissue availability. We have synthesized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their efficacy in vivo. Specifically, we studied the short- and long-term stability and biocompatibility of 12 mm long tubes for the repair of surgically created 10 mm nerve gaps in rat sciatic nerves.