Jejunal Dieulafoy lesion with intraintestinal calcification on computerized tomography: A case report.

RATIONALE: A Dieulafoy lesion is a rare cause of gastrointestinal (GI) bleeding, especially in the jejunum, and the presence of calcifications on CT might be suspicious of the diagnosis. PATIENT CONCERNS: We describe a 72-year-old woman with anemia and melena. Hemoglobin was 6.0 g/dL, and the stools were positive for occult blood (4+). Blood pressure was 116/54 mm Hg. Physical examination showed pale face and pitting edema in both lower limbs. Abdominal computerized tomography showed calcification in the small intestine of the left lower abdomen. Capsule endoscopy showed a blood clot. DIAGNOSES: Dieulafoy lesion. INTERVENTIONS: Single balloon endoscopy was performed via the oral approach and showed a blood clot on the suspected submucosal tumor of jejunum. A hemostatic clip was placed at the base of the lesion to allow the surgeon to locate it during the operation. Laparoscopy was performed, and the lesion was resected. OUTCOMES: The postoperative pathology showed a Dieulafoy lesion. The lower extremity edema subsided. GI bleeding did not recur over 1 year of follow-up, and hemoglobin was 12.2 g/dL. A Dieulafoy lesion is a rare cause of GI bleeding, and it is even rarer in the jejunum. LESSONS: A Dieulafoy lesion does not have special imaging features, but the presence of calcifications in the small intestine on computerized tomography might be suspicious of the diagnosis. When endoscopic treatment is difficult, surgical treatment could be considered.

Bilateral and multiple sub-internal limiting membrane hemorrhages in a familial retinal arteriolar tortuosity patient by Valsalva-like mechanism: an observational case report.

BACKGROUND: Bilateral and multiple Valsalva-related sub-internal limiting membrane (ILM) hemorrhages in a familial retinal arteriolar tortuosity (FRAT) patient is rare, and we treated this patient by both observation and Neodymium yttrium aluminum garnet (Nd: YAG) laser membranotomy methods. CASE PRESENTATION: A 13-year-old female student presented with sudden visual loss and central scotoma in both eyes after running 800 m at the school gym. The examination revealed six sub-ILM hemorrhages with the biggest hemorrhage measuring approximately 1.5-disc diameters (DD) in the right eye and two sub-ILM hemorrhages with the biggest one measuring 5.5 DD in the left eye. The patient was diagnosed as having Valsalva retinopathy associated with FRAT. Nd: YAG laser membranotomy was performed at the biggest hemorrhages and the rest hemorrhages were treated with observation in both eyes. The visual acuity recovered to 20/16 in the right eye and 20/20 in the left eye. Epiretinal membrane (ERM) formation was observed in the left eye. CONCLUSIONS: Nd: YAG laser could be considered for treating premacular hemorrhage in FRAT patient especially when a quick vision recovery was needed. This is the first reported case of a FRAT patient suffering from bilateral and multiple Valsalva-related sub-ILM hemorrhages which were treated by both observation and Nd: YAG laser treatment.

Corkscrewing of retinal arterioles leading to diagnosis of coarctation of aorta.

Coarctation of aorta (CoA) usually leads to elevation of blood pressure above the site of obstruction and this elevated blood pressure probably gets transferred and is reflected in the retinal arterioles producing certain signs of hypertensive retinopathy. Fundus examination helps in differentiating hypertension due to CoA from other causes of juvenile hypertension, as corkscrewing of retinal arterioles is seen only in CoA but not in other conditions. A 16 year hypertensive male who was on antihypertensive treatment presented for routine checkup. On examination his visual acuity was 6/6 in both eyes. Funduscopy of both eyes revealed a normal optic disc with generalised narrowing of arterioles and broadened light reflex. The arterioles showed corkscrew tortuosity (U shaped arterioles). Based on the fundus findings, CoA was suspected and the patient was referred for cardiac evaluation. Echocardiogram revealed post ductal CoA. In juvenile hypertension, careful examination of the fundus can provide a clue to the systemic diagnosis and this case highlights the importance of ophthalmoscopic examination in diagnosing a potentially fatal systemic disease.

Pulmonary vascular development in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterised by a diaphragmatic defect, persistent pulmonary hypertension (PH) and lung hypoplasia. The relative contribution of these three elements can vary considerably in individual patients. Most affected children suffer primarily from the associated PH, for which the therapeutic modalities are limited and frequently not evidence based. The vascular defects associated with PH, which is characterised by increased muscularisation of arterioles and capillaries, start to develop early in gestation. Pulmonary vascular development is integrated with the development of the airway epithelium. Although our knowledge is still incomplete, the processes involved in the growth and expansion of the vasculature are beginning to be unravelled. It is clear that early disturbances of this process lead to major pulmonary growth abnormalities, resulting in serious clinical challenges and in many cases death in the newborn. Here we provide an overview of the current molecular pathways involved in pulmonary vascular development. Moreover, we describe the abnormalities associated with CDH and the potential therapeutic approaches for this severe abnormality.

Lesão de Dieulafoy do fundo gástrico / Dieulafoys lesion of the gastric fundus

Hemorragia digestiva alta (HDA) é uma emergência clínica exteriorizada através de melena, hematêmese, além de alterações hemodinâmicas decorrentes de perda volêmica. Existem vários diagnósticos etiológicos causadores de hemorragias digestivas altas; dentre eles, uma causa rara é lesão de Dieulafoy, sendo relacionada acerca de 2% dos casos de HDA. Neste relato, descreveremos um caso de lesão de Dieulafoy, evidenciando a relevância desta lesão como um importante diagnóstico diferencial nas causas de hemorragia digestiva alta. O procedimento diagnóstico e o manejo atual são fundamentados pela endoscopia digestiva alta. A hemostasia endoscópica é realizada, utilizando técnicas como eletrocoagulação, injeções com adrenalina e hemoclips.

Upper gastrointestinal bleeding (UGBI) is a clinical emergency externalized through melena, hematemesis and hemodynamic changes due to volume loss. There are a lot of etiological diagnosis of gastroduodenal hemorrhages, including Dieulafoy which is a rare cause related about 2% of the UGBI cases. In this report we describe a case of Dieulafoy lesion highlighting the importance of this lesion as a rare and important differential diagnosis in cases of upper gastrointestinal bleeding. The current diagnostic and management is justified by endoscopy. Endoscopic hemostasis is performed using techniques such as electrocoagulation, injections of adrenaline and hemo-clips.

The efficiency of endoclips in maintaining the gastrointestinal bleeding-related Dieulafoy's lesion.

BACKGROUND: Dieulafoy's lesion (DL) is a relatively uncommon medical condition characterized by a large tortuous arteriole in the submucosa of any part of gastrointestinal (GI) tract wall that bleeds via erosion likely caused in the submucosal surface by protrusion of the pulsatile arteriole. Compared with other endoscopic hemostatic techniques, clipping alone for DL is limited. AIMS: The aim of the present case series study is to identify common clinical and endoscopic features, rates of occurrence, to review the outcome of endoscopic management of upper GI tract DL, and to illustrate the use and the efficiency of endoclips in maintaining the GI bleeding due to DL. PATIENTS AND METHODS: This case series was conducted at Department of Gastroenterology, Diskapi Yildirim Beyazit Educational and Research Hospital. The patients who were admitted to the emergency department of Diskapi Yildirim Beyazit Educational and Research Hospital underwent gastrointestinal system (GIS) endoscopy between 2008 and 2013 and were assessed retrospectively. Five cases of GI bleeding related to DL were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated. RESULTS: The median number of endoscopic hemoclips application in first endoscopy was 4 (2-9). Rebleeding developed in all patients who had hemoclips applied. Re-endoscopy was performed in three of these patients, which controlled the bleeding. Two patients were transferred to surgery. CONCLUSIONS: Combination of endoscopic injection and mechanical therapies seems a suitable method for maintaining upper GIS bleeding due to DL. Also, further studies are needed to better define the best endoscopic approach for the treatment of DL.

Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity.

OBJECTIVES: Our aim was to determine the molecular cause of autosomal dominant familial retinal arteriolar tortuosity (FRAT) in a family with three affected subjects. MATERIAL AND METHODS: Ophthalmologic evaluation included determination of best-corrected visual acuity (BCVA), slit-lamp and dilated fundus inspection, applanation tonometry, fundus photography, and fluorescein retinal angiography (FA). Molecular methods included whole exome sequencing analysis and Sanger sequencing validation of putative causal mutation in DNA from affected individuals. RESULTS: Typical signs of familial retinal arteriolar tortuosity were observed in all three patients. Exome sequencing identified a heterozygous c.1528G > A (p. Gly510Arg) mutation in COL4A1. Sanger sequencing confirmed that all three patients harbored the same pathogenetic mutation in COL4A1. The p. Gly510Arg variant in COL4A1 was absent in DNA from an available unaffected daughter, from a set of control alleles, and from publicly available databases. CONCLUSIONS: The molecular basis of familial retinal arteriolar tortuosity was identified for the first time, thus expanding the human phenotypes linked to COL4A1 mutations. Interestingly, the COL4A1 p.Gly510Arg mutation has been previously identified in a family with HANAC (Hereditary Angiopathy with Nephropathy, Aneurysm and Cramps), a multisystemic disease featuring retinal arteriolar tortuosity. No cerebral, neurologic, renal, cardiac or vascular anomalies were recognized in the pedigree described here. These data indicate that identical mutations in COL4A1 can originate both eye-restricted and systemic phenotypes.

Association of parental blood pressure with retinal microcirculatory abnormalities indicative of endothelial dysfunction in children.

OBJECTIVE: Microcirculatory abnormalities precede the onset of hypertension and may explain its familial nature. We examined the relationship between parental blood pressure (BP) and offspring retinal microvasculature in Pakistani trios [father, mother, and child (aged 9-14 years)]. METHODS: This is a substudy of a population-based trial of BP reduction. Data were available on 358 normotensive, and 410 offspring of at least one hypertensive parent. Retinal vessel characteristics were measured from digital images. Multivariable linear regression models were built to assess the associations between maternal and paternal BP and offspring retinal microvasculature. RESULTS: Optimality deviation was greatest in offspring of two hypertensive parents, compared with those with one or no hypertensive parent (P=0.030 for trend). Paternal SBP and DBP were each significantly associated with optimality deviation in offspring (P=0.023 and P=0.006, respectively). This relationship persisted after accounting for offspring cardiovascular risk factors [increase in optimality deviation (95% confidence interval, CI) 0.0053 (0.0001-0.0106, P=0.047) and 0.0109 (0.0025-0.0193, P=0.011), for each 10 mmHg increase in paternal SBP and DBP, respectively]. Maternal DBP was inversely associated with offspring arteriovenous ratio -0.0102 (-0.0198 to -0.0007, P=0.035). CONCLUSION: Microvascular endothelial dysfunction in children is associated with increasing levels of parental hypertension. The association with paternal BP is independent of other cardiovascular risk factors, including the child's BP. Higher maternal DBP is associated with evidence of arteriolar narrowing in offspring. These early microcirculatory changes may help explain familial predisposition to hypertension in people of Pakistani origin at an early age. VIDEO ABSTRACT: :

Arterial embolization of a bleeding gastric Dieulafoy lesion: a case report.

Dieulafoy's lesion is one of an unusual cause of upper gastrointestinal bleeding (U GIB). Endoscopic intervention has always been a preferred non-surgical method in treating UGIB including bleeding from Dieulafoy's lesion. Owing to recent advances in angiography, arterial embolization has become a popular alternative in non- variceal UGIB especially in cases with failed endoscopic treatment. However, managing bleeding Dieulafoy's with selective arterial embolization as the first line of treatment has not been exclusively practiced. We hereby, report a case of bleeding Dieulafoy lesion which had been primarily treated with arterial embolization.

Surgery for a gastric Dieulafoy's lesion reveals an occult bleeding jejunal diverticulum. A case report.

BACKGROUND: Jejunal diverticulosis is an uncommon disease and usually asymptomatic. It can be complicated not only by diverticulitis, but by hemorrhage, perforation, intussusception, volvulus, malabsorption and even small bowel obstruction due to enteroliths formed and expelled from these diverticula. METHODS: We describe a case of an occult bleeding jejunal diverticulum, casually discovered in a patient that was taken to surgery for a Dieulafoy's lesion after unsuccessful endoscopic treatment. We performed a gastric resection together with an ileocecal resection.Macroscopic and microscopic examinations confirmed the gastric Dieulafoy's lesion and demonstrated the presence of another source of occult bleeding in asymptomatic jejunal diverticulum. DISCUSSION: The current case emphasizes that some gastrointestinal bleeding lesions, although rare, can be multiple and result in potentially life-threatening bleeding. The clinician must be mindful to the possibility of multisite lesions and to the correlation between results of the investigations and clinical condition of the bleeding patient.

High interstitial fluid pressure is associated with tumor-line specific vascular abnormalities in human melanoma xenografts.

PURPOSE: Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks. MATERIALS AND METHODS: A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array. RESULTS: High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. CONCLUSIONS: High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities.

Preliminary ocular histopathological observations on heterozygous NEMO-deficient mice.

The majority of patients with incontinentia pigmenti (IP) have a mutation in the nuclear factor-kappa-beta essential modulator (NEMO) gene, and mice with a targeted deletion of NEMO exhibit skin pathology remarkably similar to the human disease. This study characterizes the retinal vascular abnormalities of NEMO-deficient mice, and compares this phenotype to known features of human IP. Nineteen heterozygous NEMO-deficient female mice, ages ranging from post-natal day 8 (P-8) through 6.5 months of life, were studied. Eyes were sectioned and stained either whole or as retinal flat mounts after incubation for enzyme histochemical demonstration of ADPase, which labels the vasculature. With maturation, retinal arteriolar abnormalities became evident at 3 months of age. Global assessment of the retinal vasculature with ADPase staining showed increased vascular tortuosity. Microscopic examination of sections of ADPase-incubated retinas revealed arteriolar luminal narrowing due to endothelial cell hypertrophy and increased basement membrane deposition. Venous morphology was normal. This study characterized the histological retinal phenotype of heterozygous NEMO-deficient female mice. Most striking were retinal arteriolar abnormalities, including luminal narrowing, endothelial cell hypertrophy, and basement membrane thickening. Retinal flat mounts revealed arteriolar tortuosity without evidence of vaso-occlusion or neo-vascularization.

Retinal arterial abnormalities correlate with brain white matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.

PURPOSE: The aim of this study is to determine the relationship between retinal abnormalities and brain white matter hyper-intensities (WMH) in symptomatic patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). METHODS: Fifteen patients with CADASIL and fifteen age-matched healthy control individuals were enrolled in this study. Ophthalmological examinations were performed on all subjects and all patients with CADASIL underwent cerebral MRI scanning. Retinal artery abnormalities were graded according to the Keith-Wagener-Barker hypertensive retinopathy classification. WMH were classified as punctuate (Grade 1), nodular or early confluent (Grade 2) and diffusly confluent (Grade 3). Partial correlation was used to assess the relationship between retinal abnormalities and WMH, controlling for age. RESULTS: Retinal arteriole narrowing existed in 15 cases and 2 controls, with Grade 2 and Grade 3 being the most common grading of retinal artery narrowing in patients with CADASIL. All patients had WMH on MRI, rated as Grade 1 in one patient, Grade 2 in five patients and Grade 3 in nine patients. The correlation coefficient of retinal arteriole narrowing and WMH was 0.546 (P < 0.05). CONCLUSION: Retinal arteriole narrowing may be associated with the severity of the cerebral lesions in CADASIL.

The effects of binge alcohol exposure in the 2nd trimester on the estimated density of cerebral microvessels in near-term fetal sheep.

Heavy fetal alcohol exposure is associated with a spectrum of neurological abnormalities, although the mechanism of injury is largely unknown. We previously reported attenuated cerebral blood flow response to hypoxia in fetal and newborn sheep which were exposed to alcohol earlier in pregnancy. One possible mechanism for this effect of alcohol on the developing cerebral vasculature is a decrease in cerebral microvessel density, similar to its effect on developing neurons. Therefore, we tested the hypothesis that prenatal alcohol exposure decreases cerebral microvessel density. Pregnant ewes received intravenous infusions of ethanol or saline during days 60-84 of gestation (term=150 days) and at 125 days of gestation we obtained the fetal brains for study. We immunohistochemically labeled vessels of the left cerebral forebrain hemispheres with antibody to endothelial nitric oxide synthase and then obtained unbiased stereological estimates of cerebral microvessel density using a modified optical fractionator method. We studied 20 fetal brains of which 9 were alcohol-exposed, 11 were saline-controls, and all were products of a twin gestation. Although brain and body weights were not different between groups, the alcohol-exposed group had significantly lower brain weight as a percentage of body weight. Estimates of cerebral microvessel density were not significantly different between alcohol-exposed and saline-control groups: 12.7+/-8.7 and 9.1+/-2.8 microvessels per mm(3), respectively (mean+/-SD, p=0.32). Since there is no change in estimated cerebral microvessel density after prenatal alcohol exposure, we conclude that decreased cerebral microvessel density is not a likely explanation for attenuated cerebral blood flow in response to hypoxia.

The netrin receptor UNC5B promotes angiogenesis in specific vascular beds.

There is emerging evidence that the canonical neural guidance factor netrin can also direct the growth of blood vessels. We deleted the gene encoding UNC5B, a receptor for the netrin family of guidance molecules, specifically within the embryonic endothelium of mice. The result is a profound structural and functional deficiency in the arterioles of the placental labyrinth, which leads first to flow reversal in the umbilical artery and ultimately to embryonic death. As this is the only detectable site of vascular abnormality in the mutant embryos, and because the phenotype cannot be rescued by a wild-type trophectoderm, we propose that UNC5B-mediated signaling is a specific and autonomous component of fetal-placental angiogenesis. Disruption of UNC5B represents a unique example of a mutation that acts solely within the fetal-placental vasculature and one that faithfully recapitulates the structural and physiological characteristics of clinical uteroplacental insufficiency. This pro-angiogenic, but spatially restricted requirement for UNC5B is not unique to murine development, as the knock-down of the Unc5b ortholog in zebrafish similarly results in the specific and highly penetrant absence of the parachordal vessel, the precursor to the lymphatic system.

Acroangiodermatitis.

A 26-year-old man with a history of chronic primary lymphedema of the left lower extremity presented with elephantiasis, confluent, violaceous, mascerated plaques, and ulcers on the dorsal aspects of the toes of the left foot. Histopathologic examination showed a proliferation of small blood vessels associated with extravasated erythrocytes and hemosiderin deposits consistent with the diagnosis of acroangiodermatitis. Treatment of the focal ulcers includes compression therapy, local wound care, and surgical elimination of the shunt if there is an associated arteriovenous malformation.