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VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues.

Recently, vascular endothelial growth factor receptor 3 (VEGFR-3) has been shown to provide a specific marker for lymphatic endothelia in certain human tissues. In this study, we have investigated the expression of VEGFR-3 and its ligands VEGF-C and VEGF-D in fetal and adult tissues. VEGFR-3 was consistently detected in the endothelium of lymphatic vessels such as the thoracic duct, but fenestrated capillaries of several organs including the bone marrow, splenic and hepatic sinusoids, kidney glomeruli and endocrine glands also expressed this receptor. VEGF-C and VEGF-D, which bind both VEGFR-2 and VEGFR-3 were expressed in vascular smooth muscle cells. In addition, intense cytoplasmic staining for VEGF-C was observed in neuroendocrine cells such as the alpha cells of the islets of Langerhans, prolactin secreting cells of the anterior pituitary, adrenal medullary cells, and dispersed neuroendocrine cells of the gastrointestinal tract. VEGF-D was observed in the innermost zone of the adrenal cortex and in certain dispersed neuroendocrine cells. These results suggest that VEGF-C and VEGF-D have a paracrine function and perhaps a role in peptide release from secretory granules of certain neuroendocrine cells to surrounding capillaries.

Adult↗

Optic nerve sheath fenestration for a reversible optic neuropathy in radiation oncology.

To the authors' knowledge, there is a paucity of published accounts of management of radiation-induced optic neuropathy (RION) by optic nerve sheath fenestration (ONSF) in the conventional medical literature. With higher doses of radiation being given by using conformal techniques, more radiation-induced optic neuritis and neuropathy will be identified. We report here the successful use of ONSF to restore vision to three consecutive patients with pending anterior RION, and the importance of early identification and intervention in these potentially reversible cases.

Adult↗

Fenestrated sagittal sinus mimicking posterior cerebral infarction.

Two patients who presented with abnormal neurological findings and focal abnormalities on static brain imaging, were felt to have infarction in the distribution of the posterior cerebral artery. However, the posterior flow study delineated the cause of the abnormality as being a fenestrated anomaly of the sagittal sinus. The incidence of occlusive disease of the posterior cerebral artery, its clinical and scintigraphic presentation and the potential pitfalls for misinterpretation are reviewed.

Brain↗

Office-based insertion of pressure equalization tubes: the role of laser-assisted tympanic membrane fenestration.

OBJECTIVE: To describe the role of the hand-held otoscope combined with a flashscanner CO2 laser, OtoLAM (ESC/Sharplan, Yokneam, Israel), for pressure equalization tube (PET) insertion in an office setting. STUDY DESIGN: Prospective, multisite, clinical cohort trial (Institutional Review Board approved; informed consent) in the setting of pediatric otolaryngology outpatient departments at four tertiary care children's hospitals. METHODS: Selected for the study were 54 patients (96 ears), ages 6 months to 23 years, who met standard indications for PET insertion using cold-knife myringotomy and tube insertion under general anesthesia. PETs were indicated for recurrent otitis media, chronic otitis media with effusion, and eustachian tube dysfunction-all unresponsive to medical therapy. Topical anesthesia was achieved with iontophoresis (n = 1) or topical anesthesia: 8% tetracaine on an Otowick (Xomed Surgical Products, Jacksonville, FL, catalogue No. 400141) against the tympanic membrane for 45 to 180 minutes (n = 53). Laser-assisted tympanic membrane fenestration was performed with the OtoLAM set at single pulse, 2.0- to 2.6-mm spot size, and between 3 and 18 W. Insertion of grommets was accomplished using the otomicroscope and an "alligator" microforceps. Restraints with papoose were used in 79% of children with a mean age of 34.4 months (SD = 60.9 mo). Clinical, parent/patient, and physician satisfaction and comparative cost impact outcomes are described. RESULTS: All ears but three (3%) underwent successful placement of a PET. Pain was described as "absent" in 39%, "present but tolerable" in 30%, and "severe" in 30% of children at the time of procedure; 5 minutes after the procedure pain was described as "absent" in 75%, "present but tolerable" in 22%, and "severe" in 3%. Tube plugging (3 of 74 available ears; 4%) or persistent otorrhea (1 of 74 ears; 1.4%) occurred infrequently at the 1-month follow-up. Before PET insertion, hearing loss was noted in 66% of cases (mild, 38%; moderate, 22%; and severe, 6%). Mild hearing loss was noted in only 8% and moderate hearing loss in 2% of 47 (50%) of the ears at the 3-month follow-up. Ninety-two percent of parents were highly satisfied with the procedure in preference to PETs in the operating room under general anesthesia, and 97% preferred OtoLAM with PET insertion, rather than further courses of antibiotics; only one parent would rather have had the PET insertion under general anesthesia. Cost savings to health care organizations, particularly payers, and to parents are substantial (32%-48%) and warrant attention. Cost to the physician is manageable only if an appropriate approach to the third party payers results in a substantial increase in reimbursements. CONCLUSIONS: The data indicate excellent clinical effectiveness, reduced risk, and high parent and physician satisfaction. Strong incentives for physicians to use this technique are in all stakeholders' best interests. These incentives need to evolve as soon as possible for the more widespread acceptance of OtoLAM with PET insertion in an office setting for appropriately selected patients.

Adolescent↗

Fenestration of vertebral artery at the craniovertebral junction in Down syndrome: a case report.

STUDY DESIGN: Case report of a Down syndrome patient with right vertebral artery fenestration and abnormalities of the craniovertebral junction. OBJECTIVES: Describe the utility of 3-dimensional computed tomography angiography for evaluating vertebral artery anomalies before surgery. SUMMARY OF BACKGROUND DATA: Previous reviews evaluating catheter angiograms identified various anomalies of vertebral artery at the craniovertebral junction. The frequency of vertebral artery anomalies is increased in patients having osseous anomalies at the craniovertebral junction. Down syndrome is associated with a high incidence of bone abnormalities at the craniovertebral junction, but there have been no published reports of vertebral artery anomalies per se at the craniovertebral junction. METHODS: A 16-year-old woman with trisomy 21 presented with gait abnormalities and myelopathy in association with bone abnormalities at the craniovertebral junction, including hypoplastic odontoid and ossiculum terminale. Computed tomography angiography showed that right vertebral artery bifurcated after exiting the C2 transverse foramen with one branch passing through the C1 transverse foramen, whereas the other turned posteromedially and entered the spinal canal between C1 and C2. RESULTS: Occipito-C2 posterior fusion was performed with a rod and screw system. Intraoperatively, the course of the anomalous right vertebral artery was identified by Doppler angiography, and the surgical approach was modified to allow safe pedicle screw insertion while avoiding vertebral artery injury. After surgery, myelopathy resolved within 3 months. CONCLUSIONS: Before corrective surgery of craniovertebral junction anomalies in patients with Down syndrome, the possibility of vertebral artery anomalies associated with abnormal craniovertebral junction anatomy should be considered. With preoperative 3-dimensional computed tomography angiography, we can precisely identify the anomalous vertebral artery and modify the surgical approach to reduce the possible risk of intraoperative vertebral artery injury in advance.

Adolescent↗

Optic nerve sheath fenestration for intracranial hypertension associated with chronic inflammatory demyelinating polyneuropathy.

The authors report a case of papilledema in a 61-year-old woman with chronic demyelinating polyneuropathy. The cerebrospinal fluid protein level was elevated (2.68 to 4.51 g/L), as was the cerebro-spinal fluid opening pressure (27 to 40 cm H2O). A unilateral optic nerve sheath fenestration proved to be effective in preserving vision, and the papilledema resolved completely.

Cerebrospinal Fluid Proteins↗

Balloon fenestration of iatrogenic celiac artery dissection.

Iatrogenic dissections of the celiac artery during catheterization are rare complications. Herein a case is reported in which complete occlusion of the celiac artery occurred during transcatheter arterial chemoembolization and was immediately successfully recanalized with balloon fenestration of the intimal flap. Follow-up angiography showed patent celiac and common hepatic arteries with mild focal residual stenosis of the common hepatic artery orifice.

Aortic Dissection↗

Ultrastructure of the lesions of psoriasis vulgaris transplanted into the subcutaneous tissue of nude mice by the skin fenestrating transplantation method.

We have developed a new skin transplantation method, called the skin fenestrating transplantation method, in which the nude mouse skin covering the lesion was removed one week after the transplant was embedded. One week later, transplanted psoriatic skin was biopsied and specimens were examined by electron microscopy. The basal cells and the nuclei of transplanted psoriatic epidermis were long and slender. Projections of basal cells extended to the dermis. Erythrocytes and lymphocytes were seen in the intercellular space. In the spinous cell layer, the cytoplasm and the nuclei were round. In the cytoplasm, mitochondria and endoplasmic reticuli were abundant, and tonofibrillar formation was poor. In the upper part of the epidermis, the cells were horizontally elliptic and, in the cytoplasm, short tonofibril bundles were formed. In the uppermost layers, in the cytoplasm of flat cells, degenerated flat nuclei, low dense lipid droplets and clumps of ribosomes were observed. These findings resembled the findings of intact psoriasis lesions more closely than those obtained by the skin embedding transplantation method.

Animals↗

Transhepatic fenestration of liver cyst: a further application of laparoscopic surgery.

Surgery is indicated for the treatment of highly symptomatic liver cysts in adult polycystic liver disease. Several options are available, including liver resection, but surgical morbidity in a benign condition may be unacceptable. The authors report the transhepatic fenestration of a liver cyst under laparoscopic guidance in a 47 year old Chinese male. There was an excellent clinical outcome and minimal morbidity. Laparoscopic treatment is both effective and minimally traumatic, which is appropriate for a condition that will inevitably progress.

Cysts↗

New technique for fenestration of the interatrial septum.

Achieving controlled flow between the systemic and pulmonary venous circulations is desirable in many complex congenital heart diseases. This includes the Fontan circulation, primary pulmonary hypertension, double inlet ventricles, or hypoplastic left heart with obstruction to the atrioventricular valve. As no specific device is available for this purpose, we developed a balloon-mounted stent technique to achieve a predetermined-sized fenestration of an atrial baffle in a patient with Fontan circulation. The details of the technique are described.

Adult↗

Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor (II). Basic fibroblast growth factor and transforming growth factor beta 1.

Effects of a topically applied growth factor combination on fibroblast migration, collagen fiber formation and bone regeneration were studied in standardized periodontal defects in 4 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and into the dentin of maxillary and mandibular teeth. Collagen sponges, impregnated with 200 ng insulin-like growth factor II, 20 ng basic fibroblast growth factor and 6 ng transforming growth factor beta 1 were fitted to defects randomly in right or left quadrants and the flaps repositioned and sutured. Contralateral control defects received the collagen with vehicle only. Experimental procedures were staggered to allow observations of healing 3, 7, 10, and 14 days after surgery. Histometric analysis showed no differences in fibroblast and collagen density between control and growth factor defects. Bone regeneration was significantly greater in control than in growth factor defects 10 and 14 days after surgery. The rate of healing generally appeared more affected by intra-dog variations or procedural variations than by the growth factor combination.

Alveolar Process↗

Collagen gel and membrane in guided tissue regeneration in periodontal fenestration defects in dogs.

The effect of a collagen gel matrix as a submembranous space-maintaining material was evaluated in guided tissue regeneration procedures. In 4 dogs, contralateral surgical circular fenestration defects, 5 mm in diameter, were produced at the midbuccal aspect of the alveolar bone in 8 maxillary canines. Removal of bone, PDL and cementum was complete. Experimental sites were filled with collagen gel and covered with collagen membranes; control sites were covered with collagen membranes and the underlying space was spontaneously filled with blood. Mucogingival flaps were repositioned. Histological and histomorphometric observations, 6 weeks post-surgery, indicated that defects covered by collagen membranes presented the most impressive regeneration with almost complete coverage of the denuded root by new cementum (98.4%) and new bone (63.2%). In the experimental defects, 83.5% coverage of new cementum with only 21.9% new bone regeneration was observed. These results suggest that collagen gel, interfered with healing by PDL and bone-derived cells in the submembranous space.

Alveolar Bone Loss↗

Management of disc-associated wobbler syndrome with a partial slot fenestration and position screw technique.

A previously unpublished surgical technique for the management of disc-associated wobbler syndrome is described. A series of 17 middle-aged dobermanns (mean age 7.4 years) with this condition were managed by a technique of partial slot fenestration and position screw fixation of the affected disc space (C6/7 in all cases). One patient was lost to follow-up and, of the remaining 16 cases, 13 improved following surgery (81 per cent). The three failures were a consequence of incorrect placement of one of the screws. Careful evaluation of immediate postoperative radiographs allows this problem to be identified; the screw can then be correctly repositioned with an immediate return to surgery.

Animals↗

Permeability of the fenestrated capillaries in the cat submandibular gland to lipid-insoluble molecules.

1. Permeability-surface area products for the fenestrated capillaries in the perfused cat submandibular gland have been measured for graded lipid-insoluble molecules using the single-passage, multiple-tracer dilution technique. 2. The permeability-surface area for [57Co]cyanocobalamin (mol. wt. 1353) increased as the perfusion flow was increased, but reached a constant value of 4.11 +/- 0.25 ml.min-1.g-1 (mean +/- S.E., n = 9) at flows above 8 ml. min-1.g-1. For [125I]insulin (approximate mol. wt. 6000) it was 1.80 +/- 0.13 ml.min-1.g-1 (mean +/- S.E., n = 9) and apparently diffusion-limited at all the high flow rates studied. A similar permeability-surface area product was measured for [14C]inulin (mol. wt. 5500): 1.76 +/- 0.10 (mean +/- S.E., n = 4). 3. Permeability-surface area values for cyanocobalamin and insulin in the salivary gland are respectively about 20 and 200 times larger than the estimates reported for the continuous capillaries of cardiac and skeletal muscle. 4. The permeability-surface area (PS) ratio [57Co]cyanocobalamin/[125I]insulin (2.33 +/- 0.15, mean +/- S.E., n = 9) was significantly greater than the apparent ratio of their free diffusion coefficients (1.76), suggesting restricted diffusion of insulin relative to cyanocobalamin across the capillary endothelium. 5. Permeability-surface area products for the smaller molecular weight tracers (22Na, 86Rb and 51Cr-EDTA (mol. wt. 357)) increased continuously with perfusion rate, indicating flow-limited solute exchange. The PS ratio of Rb/EDTA was close to unity whereas the corresponding free diffusion ratio is 3.85. 6. The high permeability-surface area values measured were thought to be associated with the fenestrae which appeared to act as high concentrations of 'small pores' rather than as 'large pores'.

Animals↗

Effect of fluid pressure on the hydraulic conductance of interstitium and fenestrated endothelium in the rabbit knee.

A synovial cavity is separated from plasma by synovial intima in series with capillary endothelium. Because 20% of the intimal surface is bare interstitium, the system is a convenient model for the study of passive transport through serial endothelial and interstitial layers. Here hydraulic flow across the composite barrier was investigated in forty-seven knees of isolated, blood-perfused rabbit hindquarters, at intra-articular pressures between 4 and 30 cmH2O. In order to measure barrier conductance at constant intra-articular pressure, pressure on the opposite side of the barrier was varied, i.e. capillary blood pressure (PC). Capillary pressure was changed by alteration of vascular perfusion pressures, and the resulting changes in rate of absorption of Krebs solution from the synovial cavity (QS) were recorded. Trans-synovial absorption was a negative linear function of PC at each joint pressure, in verification of the applicability of Starling's hypothesis to this system. The hydraulic conductance of the blood-joint barrier was calculated as dQS/dPC. Conductance was independent of intra-articular pressure below 9 cmH2O and was 0.12 +/- 0.015 microliter min-1 mmHg-1 (mean +/- S.E. of mean). Barrier conductance increased as a curvilinear function of intra-articular pressure above 9.4 cmH2O (yield pressure). At 30 cmH2O conductance averaged 0.60 +/- 0.06 microliter min-1 mmHg-1, a 5-fold increase. A hyperbolic curve relating net barrier conductance to joint pressure was predicted from the hypothesis that interstitial conductance increases as a monotonic function of intra-articular pressure above yield pressure (Appendix). The data were in reasonable agreement with the theoretical hyperbola. Interstitial conductivity (3 X 10(-7)-7 X 10(-7) cm4 s-1 N-1 below yield pressure) and mean endothelial conductance (1.1 X 10(-4)-1.4 X 10(-4) cm3 s-1 N-1) were evaluated and compared with values in other tissues. Synovial endothelium contains on average 0.25 fenestrae micron-1 circumference. The conductance of a single fenestra was calculated to be 2.3 X 10(-13) cm5 s-1 N-1. Interstitial resistance accounted for roughly half the total resistance below yield point: therefore dQS/dPC should not be equated with 'capillary filtration capacity' in tissues with dense or fenestrated capillary beds. Large inconsistencies between interstitial conductivity and glycosaminoglycan concentration are noted, and mechanistic explanations of increases in conductivity with joint pressure are offered.

Animals↗

Oncotic pressures opposing filtration across non-fenestrated rat microvessels.

We hypothesized that ultrafiltrate crossing the luminal endothelial glycocalyx through infrequent discontinuities (gaps) in the tight junction (TJ) strand of endothelial clefts reduces albumin diffusive flux from tissue into the 'protected region' of the cleft on the luminal side of the TJ. Thus, the effective oncotic pressure difference (sigma black triangle down pi) opposing filtration is greater than that measured between lumen and interstitial fluid. To test this we measured sigma black triangle down pi across rat mesenteric microvessels perfused with albumin (50 mg ml(-1)) with and without interstitial albumin at the same concentration within a few micrometres of the endothelium as demonstrated by confocal microscopy. We found sigma black triangle down pi was near 70% of luminal oncotic pressure when the tissue concentration equalled that in the lumen. We determined size and frequency of TJ strand gaps in endothelial clefts using serial section electron microscopy. We found nine gaps in the reconstructed clefts having mean spacing of 3.59 microm and mean length of 315 nm. The mean depth of the TJ strand near gaps was 67 nm and the mean cleft path length from lumen to interstitium was 411 nm. With these parameters our three-dimensional hydrodynamic model confirmed that fluid velocity was high at gaps in the TJ strand so that even at relatively low hydraulic pressures the albumin concentration on the tissue side of the glycocalyx was significantly lower than in the interstitium. The results conform to the hypothesis that colloid osmotic forces opposing filtration across non-fenestrated continuous capillaries are developed across the endothelial glycocalyx and that the oncotic pressure of interstitial fluid does not directly determine fluid balance across microvascular endothelium.

Albumins↗

Modified technique of stent fenestration of the atrial septum.

OBJECTIVES: To develop a modified technique for stenting the atrial septum in the treatment of patients with a failing Fontan operation or pulmonary hypertension. SETTING: Two tertiary referral centres. STUDY DESIGN: Prospective collaborative clinical study. PATIENTS AND METHODS: A stent was mounted on a standard valvoplasty balloon catheter which was constricted to a predefined diameter by a loop created from a temporary pacing wire. Full balloon inflation created a diabolo shaped stent configuration. The technique was employed in 12 consecutive patients to relieve symptoms of a failing Fontan circulation (n = 6) or severe pulmonary hypertension (n = 6). RESULTS: Ex vivo studies confirmed that a diabolo shaped stent configuration could be achieved using the above technique. Transcatheter stent implantation was successful in all 12 patients. All six Fontan patients showed significant clinical improvement. Right atrial pressure decreased from (mean (SD)) 16.8 (2.5) to 13.7 (1.9) mm Hg (p < 0.05), and arterial oxygen saturation from 92.8 (1.8)% to 82.7 (3.8)% (p < 0.01). Six patients underwent successful stent fenestration for treatment of pulmonary hypertension. All stents were patent and stable at the most recent follow up (mean 1.75 (1.05) years). No early or late stent related complications were encountered. CONCLUSIONS: This new technique allows placement of a diabolo shaped stent with a predefined diameter across the atrial septum. The diabolo shape increases stent stability, facilitates recrossing of the stent during future catheter interventions, and ensures medium term stent patency.

Adolescent↗