Different ophthalmic artery origins: Embryology and clinical significance.

This retrospective study gives a summary of ophthalmic artery (OA) variations to serve as guidelines for surgical interventionists and trainees. Pubmed and Medline searches were conducted. The OA usually arises intradurally (superomedial, anteromedial, or rarely superolateral) from the internal carotid artery (ICA). Rare extradural origin (primitive dorsal OA) (PDOA) remnant and extremely rare interdural origin (primitive ventral OA) (PVOA) remnant are of significance when sectioning the dural ring. Rarely, a persistent PDOA with ICA origin, or a PDOA remnant with inferolateral trunk origin, enters the orbit via the superior orbital fissure (SOF) for sole or partial orbital supply. Extremely rare, the PDOA and PVOA persist and form double OAs that arise from the ICA and run via the SOF and optic foramen. Occasionally, the OA arises from the middle meningeal artery (MMA), when both the PDOA and VDOA regress and enter the orbit via the SOF. Sole orbital supply via the external carotid artery (ECA), i.e. meningo-ophthalmic artery and/or MMA branches, or dual OAs (ECA and ICA origins) may occur. Other rare OA origins include anterior or posterior communicating artery; anterior or middle cerebral artery; basilar artery; posterior inferior cerebellar artery; and the carotid bifurcation. Primitive arteries (persistent or remnant), and/or abnormal anastomoses play pivotal roles in manifestations of OA variations. Of clinical importance are orbital collateral routes and dangerous extracranial-intracranial anastomoses. Awareness of OA origins and collateral routes is imperative for transarterial embolizations or infusion chemotherapy in the ECA territory to prevent visual complications.

Imaging of dual ophthalmic arteries: identification of the central retinal artery.

Identification of the origin of the central retinal artery (CRA) is imperative in tailoring angiographic studies to resolve a given clinical problem. A case with dual ophthalmic arteries (OAs), characterized by different origins and distinct branching patterns, is documented for training purposes. Pre-clinical diagnosis of a 9-year-old child who presented with a sharp wire in the left-side eyeball was primarily corneal laceration. For imaging, a selected six-vessel angiographic study with the transfemoral approach was performed. Embolization was not required and the wire could be successfully removed. Right-side OA anatomy was normal, while left-side dual OAs with external carotid artery (ECA) and internal carotid artery (ICA) origins were seen. The case presented with a left-side meningo-ophthalmic artery (M-OA) anomaly via the ECA, marked by a middle meningeal artery (MMA) (origin: Maxillary artery; course: Through foramen spinosum) with normal branches (i.e. anterior and posterior branches), and an OA variant (course: Through superior orbital fissure) with a distinct orbital branching pattern. A smaller OA (origin: ICA; course: Through optic foramen) with a distinct ocular branching pattern presented with the central retinal artery (CRA). The presence of the dual OAs and the M-OA anomaly can be explained by disturbed evolutionary changes of the primitive OA and stapedial artery during development. The surgical interventionist must be aware of dual OAs and M-OA anomalies with branching pattern variations on retinal supply, because of dangerous extracranial-intracranial anastomotic connections. It is of clinical significance that the origin of the CRA from the ICA or ECA must be determined to avoid complications to the vision.

Imaging of Unilateral Meningo-ophthalmic Artery Anomaly in a Patient with Bilateral Nasopharyngeal Angiofibroma.

A 12-year-old boy with epistaxis presented with a rare midline nasopharyngeal angiofibroma that extended lateral into the pterygoid and infratemporal fossae. Pre-operative angiography revealed bilateral prominent feeder arteries and two major anastomotic connections, and a rare left meningo-ophthalmic artery (M-OA) anomaly that was the sole path of supply to the eye. A literature search using Pubmed and Medline was conducted. For imaging, a six-vessel study (i.e. external and internal carotid and vertebral arteries on both sides) was selected. Embolization of prominent tumor feeder arteries was unsafe for tumor extirpation, but super-selective embolization of both sphenopalatine arteries was performed to control epistaxis. The M-OA anomaly that originated from the maxillary artery (MA) was marked by an ophthalmic artery (OA) variant with orbital and ocular divisions that coursed through the superior orbital fissure and optic foramen, respectively, each with distinct branching patterns, a middle meningeal artery (MMA) with normal branches (i.e. anterior and posterior branches), and two branch variations (i.e. lacrimal and meningeal branches) that originated from the anterior branch of the MMA. The lacrimal branch coursed through a cranio-orbital foramen, but the meningeal branch remained outside the orbit. The anatomy of the right OA was normal. The left M-OA anomaly was considered incidental and not tumor-related since the tumor was more prominent on the right side, and no intra-orbital infiltrations occurred. Of clinical significance is that proximal embolization of MA or MMA carries a high risk of visual impairment in cases where M-OA anomalies are the sole mode of supply to the eye.

Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study.

BACKGROUND: Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated. DESIGN: A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods. PARTICIPANTS: Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded. INTERVENTION: Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period. MAIN OUTCOME MEASURES: Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured. FINDINGS: After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI -30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI -33.00: -2.00)]. Immune enhancement could not be demonstrated. CONCLUSIONS: These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP.

Acquired cholesteatoma pathogenesis: stepwise explanations.

BACKGROUND: Since Virchow's first, 1855 publication on cholesteatoma, this disease has been the subject of extensive debate. The pathogenesis of acquired cholesteatoma is repeatedly explained on the premises of the migration, hyperplasia and metaplasia theories, but proof for the latter theory remains limited. In retrospect, there is progress toward better understanding of all the pathological mechanisms involved, as expounded in this review. DISCUSSION: The triggers for cholesteatoma onset are diverse, and may involve tympanic membrane trauma (i.e. perforation, displacement, retraction or invagination), tympanic membrane disease, and/or tympanic cavity mucosa disease. Research has revealed that cell migration is replaced under inflammatory conditions by hyperplasia, which triggers the onset of cholesteatoma. Lately, the hyperplasia theory gained prominence and circumscription of the papillary cone formation concept provided insight into cholesteatoma progression (growth and expansion). Diseased mucosa can contribute to the development of retraction pockets and cholesteatoma. The type of cholesteatoma trigger and the role of chronic inflammation during disease progression and recurrence are important in guiding clinical intervention.

Docosahexaenoic acid induces apoptosis in colorectal carcinoma cells by modulating the PI3 kinase and p38 MAPK pathways.

Numerous studies have shown that long-chain polyunsaturated fatty acids can kill cancer cells in vitro as well as in vivo, while normal cells remain unaffected. Unfortunately, the cellular and molecular mechanisms responsible for this phenomenon are still poorly understood. The aim of this study was to investigate the potential chemopreventative/antiproliferative potential of docosahexaenoic acid (DHA) in an adenocarcinoma cell line (CaCo2 cells) and to evaluate the signalling pathways modulated by it. DHA (5-50 microM) significantly inhibited cell viability in a dose-dependent manner in CaCo2 cells, while the viability of normal colon cells (NCM460 cells) was not compromised. DHA also induced apoptosis in CaCo2 cells, as indicated by increases in caspase-3 activation and poly-ADP-ribose polymerase cleavage. Signalling proteins, which include extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), Akt and p53 were analysed by Western blotting using phosphospecific and total antibodies. The protein inhibitors wortmannin (phosphoinositide 3 kinase inhibitor), PD 98059 (MEK inhibitor) and SB 203580 (p38 inhibitor) as well as silencing RNA [small interfering RNA (siRNA)] of the p38 MAPK protein, were used to investigate cross-talk between signalling pathways. DHA supplementation significantly suppressed Akt phosphorylation, which also correlated with decreased cell viability and increased apoptosis in CaCo2 cells. Furthermore, siRNA experiments suggested a possible role for p38 MAPK in the phosphorylation of p53 at Ser15, a site which is associated with DNA damage. DHA might thus exert its beneficial effects by means of increased apoptosis and suppression of the important survival-related kinase, Akt.

HPV-induced recurrent laryngeal papillomatosis: rationale for adjuvant fatty acid therapy.

The course of human papilloma virus (HPV)-induced recurrent laryngeal papillomatosis (RLP) is variable and unpredictable. Some patients experience spontaneous remission, while others suffer from aggressive growth with dire consequences. Unfortunately, HPV DNA can persist in mucosa after treatment and can be reactivated under immunosuppressive conditions. For this reason, these benign tumors are notoriously recurrent. Better understanding of lipid-driven signaling pathways during tumorigenesis and immune responses in RLP patients can contribute to improve therapeutic approaches in an attempt to obviate this disease. Based on a mountain of evidence in the literature that concerns the immunomodulatory potential of certain FAs, it is clear that there is a rationale for adjuvant FA therapy (concurrent application) in the management of RLP. Of particular importance for immune surveillance is that the Th1 pathway in RLP is down-regulated and it is advocated that conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have the ability to restore the Th1/Th2 balance. Therefore, it is proposed that adjuvant FA therapy with CLA and EPA must be included in the therapeutical regime of RLP, since they are considered excellent anti-viral and anti-tumor agents to improve immune conditions and disease outcome. Immunocompetence plays a pivotal role in the clinical course of RLP and, hence, a new direction with adjuvant FA therapy may be the key to prevent recurrence of this disease.

HPV-induced recurrent laryngeal papillomatosis: dietary fatty acid and micronutrient intakes.

Human papilloma virus (HPV)-induced recurrent laryngeal papillomatosis (RLP) is a chronic debilitating disease often encountered among children of poor socio-economic South African groups. There are a few studies and limited evidence as to what extent nutrition may contribute to this disease. To our knowledge this is the first study that gives an account of dietary FA and micronutrient intakes in RLP patients, according to food frequency questionnaires. The dietary FA profile revealed an excessive linoleic acid (LA) intake syndrome and is also marked by high palmitic acid (PA), oleic acid (OA) and SFA intakes. Research revealed that enhanced LA and PA drive, respectively, mitogenic stimuli and apoptotic resistance during tumorigenesis, whist SFAs are associated with lipid rafts, the Th1 immune response and immunosuppression. Low folate intake, a risk for HPV-infection, and low Zn intake, detrimental for lipid metabolism and immunocompetence, occurred in, respectively, 70% and 20% RLP patients. The poor correlations that were found in RLP patients between essential fatty acids (EFAs) and micronutrients, namely, Mg, Zn and Se, involved in lipid metabolism and immune responses, need proper clarification. Overall, it is plausible that the diet (poor nutrition), a shift in lipid metabolism caused by HPV- infection, environmental smoke and oxidative stress, as well as extra-esophageal acid reflux with secondary inflammation in the larynx are co-factors in the etiology of laryngeal papillomatosis, and that immunocompromised patients are subjected to recurrence. It is imperative to ensure that children with RLP receive proper nutrition and follow a healthy lifestyle to prevent disease recurrence after treatment.

HPV-induced recurrent laryngeal papillomatosis: fatty acid role-players.

Human papilloma virus-induced recurrent laryngeal papillomatosis is considered a troublesome and dangerous disease, because it can cause airway obstruction. Better understanding of metabolic pathways followed under pathological conditions can contribute to improved therapies by which growth and recurrence may be obviated. Part I of this study presents a clinically relevant total lipid fatty acid profile for papilloma cells, analyzed by gas liquid chromatography and a phosholipid red blood cell profile for RLP patients, analyzed by thin layer chromatography. In the papilloma cells virus interference with delta-6 and delta 5- desaturase activities is prevalent and the n-9 FA metabolic pathway is followed. It is plausible that up-regulated fatty acid synthase and 9 desaturase activities occur, since enhanced saturated fatty acids and monounsaturated fatty acid levels are also prevalent. High saturated fatty acid levels are known for their propensity to interfere with delta-6 and delta-5 desaturase activities and this is reflected in the blood profile of the RLP patients. It is also known that enhanced saturated fatty acid levels can contribute to enhanced cyclooxygenase-2 activity. Furthermore, cumulative oxidative stress with an oxidative burst is responsible for complete exhaustion of exogenous dietary arachidonic acid intake in these patients. The role of linoleic acid needs to be defined. The dietary intakes of lipids and micronutrients in RLP patients and a rationale for adjuvant FA therapy in the management of these patients are discussed in parts II and III of the study.

The keloid phenomenon: progress toward a solution.

For centuries, keloids have been an enigma and despite considerable research to unravel this phenomenon no universally accepted treatment protocol currently exists. Historically, the etiology of keloids has been hypothesized by multiple different theories; however, a more contemporary view postulates a multifactoral basis for this disorder involving nutritional, biochemical, immunological, and genetic factors that play a role in this abnormal wound healing. Critical to the process of preventing or managing keloids is the need to locally control fibroblasts and their activities at the wound site. In recent years, considerable evidence has accumulated demonstrating the importance of fatty acids and bioactive lipids in health and disease, especially those involving inflammatory disorders or immune dysfunction. If hypertrophic scarring and keloid formation can be argued to have significant inflammatory histories, then it is possible to postulate a role for lipids in their etiology and potentially in their treatment. This report briefly visits past views and theories on keloid formation and treatment, and offers a theoretical rationale for considering adjuvant fatty acid therapy for keloid management. Sufficient scientific evidence in support of fatty acid strategies for the prevention and treatment of keloids currently exists, which offer opportunities to bridge the gap between the laboratory and the clinic. The intent of this paper is to serve as a basic guideline for researchers, nutritionists, and clinicians interested in keloids and to propose new directions for keloid management.