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Background: Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males., Methodology: The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG., Conclusions: Females had a higher mean score than male tinnitus patients on the BDI-II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC) extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC), parahippocampal (PHC) areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC). The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional imaging studies related to tinnitus.

Tinnitus is the continuous perception of an internal auditory stimulus. This permanent sound often affects a person's emotional state inducing distress and depressive feelings changes in 6-25% of the affected population. Distress and depression are two distinct emotional states. Whereas distress describes a transient aversive state, interfering with a person's ability to adequately adapt to stressors, depressive feelings should rather be considered as a more constant emotional state. Based on previous observations in chronic pain, posttraumatic stress disorder and depression, we assume that both states are related to separate neural circuits. We used the Dutch version of the Tinnitus Questionnaire to assess the global index of distress together with the Beck Depression Inventory to evaluate the depressive symptoms accompanying tinnitus. Furthermore sLORETA analysis was performed to correlate current density distribution with distress and depression scores, revealing a lateralization effect of depression versus distress. Distress is mainly correlated with alpha 2, beta 1 and beta 2 activity of the right frontopolar cortex and orbitofrontal cortex in combination with beta 2 activation of the anterior cingulate cortex. In contrast, the more permanent depressive alterations induced by tinnitus are associated with activity of alpha 2 activity in the left frontopolar and orbitofrontal cortex. These specific neural circuits are embedded in a greater neural network, with the parahippocampal region functioning as a crucial linkage between both tinnitus related pathways.

Prior work with free-electron lasers (FELs) showed that wavelengths in the 6- to 7-µm range could ablate soft tissues efficiently with little collateral damage; however, FELs proved too costly and too complex for widespread surgical use. Several alternative 6- to 7-µm laser systems have demonstrated the ability to cut soft tissues cleanly, but at rates that were much too low for surgical applications. Here, we present initial results with a Raman-shifted, pulsed alexandrite laser that is tunable from 6 to 7 µm and cuts soft tissues cleanly-approximately 15 µm of thermal damage surrounding ablation craters in cornea-and does so with volumetric ablation rates of 2-5 × 10(-3) mm(3)/s. These rates are comparable to those attained in prior successful surgical trials using the FEL for optic nerve sheath fenestration.

Background: Neutropenic patients often develop bacterial or fungal infections not responding to broad-spectrum antibacterial or antifungal agents. Clinical efforts were made with transfusion of granulocyte concentrates; however, functions of granulocytes after multiple G-CSF stimulations and after apheresis are not yet investigated and described sufficiently., Study Design and Methods: The aim of this study was to characterize functional and immunologic variables of granulocytes in blood samples drawn from donors before and after each stimulation episode with G-CSF, in the resulting granulocyte concentrates and in the patients 8 hours after transfusion., Results: Chemotaxis was not influenced, neither by G-CSF application nor by apheresis. Multiple G-CSF stimulations enhanced oxidative burst and phagocytosis of Escherichia coli in donor granulocytes. These values returned to basal levels in granulocyte concentrates. Expression of granulocytic surface antigens was downregulated after application of G-CSF but returned to normal and in part enhanced values in concentrates. A clinically relevant increase of proinflammatory cytokines could not be detected. Leukotriene B4 production was reduced after the fourth G-CSF stimulation in the donor blood and enhanced in the granulocyte concentrate after apheresis. Results in recipients indicate that changes of granulocyte function noted in concentrates were only transient., Conclusion: Stimulation of healthy donors with repeated G-CSF injections and subsequent granulocyte apheresis does not dramatically change decisive functions of granulocytes.

The purpose of this research is to deliver free-electron-laser (FEL) pulses for intraocular microsurgery. The FEL at Vanderbilt University is tunable from 1.8 to 10.8 microm. To deliver the FEL beam we used a metallic-coated hollow-glass waveguide of 530-mum inner diameter. A 20-gauge cannula with a miniature CaF2 window shielded the waveguide from water. Open-sky retinotomy was performed on cadaver eyes. The system delivered as much as 6 x 10(5) W of FEL peak power to the intraocular tissues without damage to the waveguide or to the surgical probe.

Purpose: Goniotomy is a surgical treatment of choice to treat primary infantile glaucoma. Goniotomy has been studied in vitro in animal and human cadaver eyes with several lasers. The objective of this study was to investigate the functional and morphologic effectiveness of goniotomy with the free electron laser in comparison with conventional needle goniotomy in early congenital glaucoma rabbits., Materials and Methods: Ten rabbits with early congenital glaucoma underwent goniotomy over 100 to 120 degrees with a needle or the free electron laser. The wavelength was 6.45 microm, and the energy level ranged from 2.2 to 3.5 mJ at 30 Hz. Because most corneas were edematous in these rabbits, an Olympus 0.8-mm diameter endoscope was coupled to the laser waveguide or the needle and inserted into the anterior chamber filled with a viscoelastic material to perform the goniotomy. Intraocular pressures were followed up to 3 weeks before an acute goniotomy was performed in the contralateral eye. All eye specimens were processed for light microscopic evaluation., Results: Incision of the pectinate ligaments and underlying trabecular meshwork was visualized through the endoscope on a video monitor during the surgeries. The mean intraocular pressure decreased after free electron laser goniotomy and after needle goniotomy, and the edematous corneas became clear in some cases. Histologic study showed successful lysing of the pectinate ligaments by the free electron laser with no obvious collateral thermal damage. However, some areas of peripheral anterior synechiae occurred. Similar results were observed in needle goniotomy cases., Conclusions: The free electron laser is capable of performing goniotomy in rabbit eyes with lower intraocular pressures in treated eyes 3 weeks after surgery. The histologic results of free electron laser goniotomy are comparable to those of conventional goniotomy. The endoscope provides beneficial visualization to perform the goniotomy in eyes with edematous corneas. The rabbit with early congenital glaucoma is also a useful infantile glaucoma surgical model.

Purpose: The authors develop a simple and economical method of applying reproducible intraoperative doses of mitomycin C for glaucoma filtering surgery., Methods: A three-part protocol was developed to study several properties of half corneal light shields (HCLSs). Part A tested the amount of mitomycin C (0.4 mg/ml) absorbed, the expansion dimensions attained, and the amount released to filter paper. In part B, the in vitro release of mitomycin C to an enucleated pig eye was examined. In part C, the in vivo release during intraoperative filtering surgery was tested., Results: The amount of mitomycin C solution absorbed by the HCLSs ranged from 1.07 x 10(-2) mg to 1.19 x 10(-2) mg; expansion width ranged from 6.8 mm to 7.0 mm; expansion height ranged from 3.6 mm to 3.8 mm; expansion thickness was constant at 0.6 mm. The amount of solution released to filter paper ranged from 6.8 x 10(-3) mg to 8.6 x 10(-3) mg. The amount of solution transferred to the pig eye ranged from 1.0 x 10(-3) mg to 2.7 x 10(-3) mg. The amount of solution released in filtering surgery ranged from 2.0 x 10(-3) mg to 4.8 x 10(-3) mg., Conclusions: The contact surface area, the amount absorbed, and the amount released by each HCLS was reproducible. The uniform thickness theoretically provides a uniform distribution of mitomycin C. This method may allow standardization of intraoperative mitomycin C application, and may reduce the incidence of complications.

Purpose: We sought to demonstrate reproducibility of the noninvasive laser Doppler flowmetry technique for measuring microvascular hemodynamics of the optic nerve head in human subjects., Methods: Laser Doppler flowmetry was performed by four examiners on four human optic nerve heads during multiple sessions. Intersubject, interexaminer, intersession, and intrasession variabilities were calculated for velocity, blood volume, and blood flow (flux)., Results: Initial variability of measurements improved after 3 months' experience. The standard deviation of the intrasession variation for single readings was 18% of the velocity mean value and 24% of the flow (flux) mean value. Based on this, a sample size of 17 (power beta = 0.8, alpha = 0.05, paired t test) will demonstrate a 10% physiologic change in flux within a session if the average of five readings is used before and after the experimental perturbation. The intersession variation was 12% and 32% for velocity and flux, respectively. Because of this, a larger sample size or additional measurement sessions are required for detection of an experimental influence between two sessions. The coefficient of variation among subjects for single readings was 7% and 10% for velocity and flux, respectively., Conclusions: Reproducibility of velocity measurements is better than reproducibility of flux measurements. After experience with the method, laser Doppler flowmetry is sufficiently precise to permit feasible studies of human optic nerve head microvascular hemodynamics when physiologic perturbations are applied.

The following experiments were undertaken to determine if blood flow is maintained by autoregulation in the human optic nerve head when circulation is challenged by elevated intraocular pressure, and to determine if the presence or absence of autoregulation is universal. Laser Doppler flowmetry was used to determine the average velocity, the number of moving erythrocytes, and the volume of flow in the capillary bed of the optic disc. These parameters were measured in 10 subjects at spontaneous levels of intraocular pressure (IOP), and at pressures artificially elevated to 25, 35, 45 and 55 mm Hg with a scleral suction cup. Four subjects (two who showed autoregulation and two who did not) were studied on six additional occasions to determine consistency of the findings. In these same four subjects a second location on the disc was also measured on six occasions to determine if the IOP-effect on blood flow varied by location. Of the 10 subjects initially studied, seven maintained the baseline level of blood flow over the lower part of the range of elevated intraocular pressure (evidence of autoregulation), but showed a decline in flow by the time IOP reached 45 or 55 mm Hg. Two subjects showed a linear decline in blood flow beginning with the smallest increment of elevation of IOP (no autoregulation), and one showed an uninterpretable result. The two individuals who showed the linear decline and two of those who showed efficient autoregulation were remeasured, and each showed consistently the same pattern as before when restudied on six different occasions each. However, at a different location on their discs, autoregulation was manifest in all of these four individuals. When challenged by elevated IOP, the optic nerve head typically maintains a steady-blood flow over a range of IOP, but fails to maintain the same flow by the time IOP reaches 45 or 55 mm Hg. Some disc locations, at least in some individuals, do not show this autoregulation, but exhibit a decline in blood flow linearly related to IOP, even with the modest elevation of IOP.

Purpose: The objective of this study was to establish the ability of laser Doppler flowmetry to detect relative changes in human optic nerve head hemodynamics caused by physiologic blood gas perturbations., Methods: Laser Doppler flowmetry permits the noninvasive assessment of relative blood velocity, volume, and flow (flux) in a sample volume of the nerve head. Such measurements were performed in two groups of healthy subjects. The first group (n = 11) was tested during normal room air breathing and then while breathing 100% oxygen (isocapnic hyperoxia). The second group (n = 10) was also tested under normal conditions as well as during isoxic hypercapnia (+ 15% end-tidal carbon dioxide). Results were analyzed by paired t tests., Results: Hyperoxia created a significant 25% (p = 0.002) decrease in optic nerve head blood flow, with blood volume decreased by 9% (p = 0.095) and blood velocity reduced by 13% (p = 0.154) compared to the room air condition. During hypercapnia, optic nerve head blood flow was increased by 28% (p = 0.012), with blood volume increased by 22% (p = 0.017) and blood velocity increased by 9% (p = 0.218) as compared to the normal room air condition., Conclusion: Blood flow in the optic nerve head capillaries changes in response to hyperoxia and hypercapnia as demonstrated in the brain and retina. Laser Doppler flowmetry permits the noninvasive assessment of these responses in humans under conditions within the physiologic range.

Purpose: When patients with glaucoma require cataract surgery, combined procedures offer important advantages over cataract surgery alone. Because mitomycin C has improved the success rate of a trabeculectomy in patients at high risk for filtration failure, the authors investigated whether it also would increase the survival rate of functioning filters in combined procedures., Methods: Patients with both cataract and glaucoma underwent combined mitomycin C trabeculectomy, extracapsular cataract extraction, and intraocular lens implantation. Mitomycin C (0.5 mg/ml) was applied topically to the trabeculectomy site for 5 minutes before the cataract extraction. Intraocular pressure (IOP), visual acuity, and astigmatism were measured preoperatively and postoperatively. One-year results are available for 74 patients., Results: At 1 year, 54 (73%) of 74 patients had IOPs of 15 mmHg or less without glaucoma medications. Visual acuity was 20/40 or better in 44 (60%) of 74 patients. Ten (15%) patients had a shift of more than 2 diopters of astigmatism against the rule compared with preoperative values. No notable corneal epithelial toxicity was present. Postoperative symptomatic hypotony with the wound construction occurred in 3 (4%) of 74 patients, with 1 patient requiring surgical revision. Other potential complications of mitomycin C include endothelial toxicity (1 patient had decreased vision due to endothelial folds) and wound stability (1 patient had wound rupture after direct ocular trauma)., Conclusion: The 1-year survival rate of a functioning trabeculectomy using mitomycin C in combined glaucoma and cataract surgery is encouraging. The longer-term benefits and possible adverse effects of mitomycin C in combined procedures are unknown and continue to be investigated.

Purpose: We investigated, in nonarteritic anterior ischemic optic neuropathy, the prevalence of various systemic diseases before or at its onset and the incidence of subsequent morbidity and mortality., Methods: We investigated prospectively the presence of systemic diseases before or at the onset of nonarteritic anterior ischemic optic neuropathy in 406 patients. The information was obtained by complete medical history and physical examination. The prevalence rates of systemic diseases in young, middle-aged, and elderly groups were compared with those in the general population. We also analyzed the influence of systemic diseases on subsequent morbidity and mortality., Results: Compared with the prevalences reported in the general population, our patients in each of the three age groups showed a significantly higher prevalence of arterial hypertension (P < or = .02), diabetes mellitus (P < .01), and gastrointestinal ulcer (P < or = .02). Also, middle-aged and elderly patients showed a significantly higher prevalence of ischemic heart disease (P < .01) and thyroid disease (P < .01). Middle-aged patients had significantly higher rates of chronic obstructive pulmonary disease and cerebrovascular disease (P < or = .01). After onset of anterior ischemic optic neuropathy, patients with both arterial hypertension and diabetes mellitus had a significantly higher incidence of cerebrovascular disease (P < .01)., Conclusions: Nonarteritic anterior ischemic optic neuropathy is a multifactorial disease in which some systemic diseases may act as predisposing factors and others as precipitating factors. Patients with anterior ischemic optic neuropathy show no significant increase in mortality, but those with both arterial hypertension and diabetes mellitus have significantly (P < .01) increased incidence of cerebrovascular disease.

Objective: To diagnose the carriers and noncarriers in a family affected with Norrie disease based on molecular analysis., Design: Family members from three generations, including one affected patient, two obligate carriers, one carrier identified with linkage analysis, one noncarrier identified with linkage analysis, and one female family member with indeterminate carrier status, were examined clinically and electrophysiologically. Linkage analysis had previously failed to determine the carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene with single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing., Results: Ophthalmoscopy and electroretinographic examination failed to detect the carrier state. The affected individuals and carriers in this family were found to have a transition from thymidine to cytosine in the first nucleotide of codon 39 of the Norrie disease gene, causing a cysteine-to-arginine mutation. Single-strand conformation polymorphism analysis identified a patient of indeterminate status (by linkage) to be a noncarrier of Norrie disease., Conclusion: Ophthalmoscopy and electroretinography could not identify carriers of this Norrie disease mutation. Single-strand conformation polymorphism analysis was more sensitive and specific than linkage analysis in identifying carriers in this family.

Purpose: The purpose of this study is to determine if an endoscope would improve visualization of the anterior chamber angle and facilitate goniotomy in a surgical cloudy corneal model of primary infantile glaucoma., Methods: A 23-gauge needle coupled to a 0.8-mm diameter flexible endoscope entered the anterior chamber of porcine cadaver eyes through a corneal incision near the limbus. Internal structures were observed on a videoscreen and recorded as the needle approached and incised pectinate ligaments near Schwalbe's line. The eyes were then prepared for light microscopy and scanning electron microscopy., Results: Internal structures were clearly visualized on the videoscreen during the goniotomy. The incision of pectinate ligaments was accompanied by the iris falling back and opening of the trabecular meshwork compared with the untreated portion of the angle. This was confirmed histopathologically., Conclusions: An endoscope coaxially coupled to a goniotomy needle tip allows visualization of the anterior chamber angle during goniotomy in the pig despite the presence of a cloudy cornea. The porcine anterior chamber angle is a useful animal model for studying the surgical treatment of primary infantile glaucoma.

Although the histologic changes occurring during healing on the lumen surface of large vessel synthetic vascular grafts have been well characterized, the cells populating the interstices of microvascular grafts have not been examined in detail. Since microvascular grafts are required to provide vascular continuity under quite different physiological and hemodynamic conditions as compared with large vessel grafts, these interstitial cells within the synthetic graft material may also vary as a function of graft size. Monoclonal antibodies, light microscopy, and scanning and transmission electron microscopy were used in this study to identify the cells present within the 30-microns pores of 1-mm diameter polytetrafluoroethylene and replamineform silicone rubber grafts. Identified cells included few capillary endothelial cells enclosing erythrocytes, rare proliferating endothelial cells, few macrophages, rare foreign body giant cells, and a majority of fibroblasts. There was no evidence of smooth muscle cells or myofibroblasts within the interstices of these microvascular prostheses 12 weeks after implantation in the rabbit central ear artery. The graft types differed by the presence of foreign body giant cells and more densely packed collagen between cells in the replamineform silicone rubber graft interstices.

This study measured the hemodynamics of peripheral arterial sites in the rat, using 20 MHz pulsed ultrasonic Doppler velocimeter (PUDVM) methods. The lower extremities of 14 male Sprague-Dawley rats were studied. The targeted sites included the abdominal aorta, external iliac, proximal femoral, mid-femoral, and saphenous arteries. The hemodynamic variables of pulse period, maximum centerline velocity, lumen diameter, and mean volumetric flow were calculated interactively from temporal-spatial plots of local velocity distributions. An analysis of variance revealed significant differences between right and left sides for lumen diameter (P = 0.028) and mean volumetric flow (P less than 0.0001). The analysis showed no statistical difference for pulse period (P = 0.0836) among sites. However, three distinct groupings of sites: 1) abdominal aorta, 2) external iliac, proximal femoral, and mid-femoral arteries, and 3) saphenous artery were noted for the remaining hemodynamic variables (P less than 0.05). These results indicate that three hemodynamically distinct regions are available for microvascular research in the rat lower extremity arterial tree.

The purpose of this study was to compare interrupted and continuous suturing techniques in laboratory microarteriorrhaphy. The comparison was based on rat femoral artery hemodynamic variables, including blood velocities, lumen diameters, and calculated blood flow. These variables were calculated by an offline computer from Doppler frequency shifts that were measured by a 20-MHz pulsed ultrasonic Doppler velocity meter. No statistical difference was noted postoperatively between the interrupted and continuous techniques relative to any hemodynamic variable. Average blood flow after the interrupted (n = 12) and continuous (n = 12) techniques was 6.59 +/- 1.12 and 6.74 +/- 1.20 ml/min, respectively. The two microarteriorrhaphy techniques result in equal postoperative vessel hemodynamics in a laboratory model.

The present study tests the hypothesis that early wound healing effects blood flow after experimental microarteriorrhaphy. Hemodynamic variables were measured in the rat femoral artery prior to and 3 weeks after both interrupted and continuous microarteriorrhaphy techniques. The hemodynamic variables (blood velocities, lumen geometry, and calculated blood flow) were measured by 20-MHz pulsed ultrasonic Doppler velocity meter (PUDVM) methods. The control values (N = 22) and the 3 weeks postoperative values, for both the interrupted (N = 11) and continuous groups (N = 11), were not statistically different (P greater than .01). The average calculated blood flows were as follows: control group 10.85 +/- 1.45 cc/min, interrupted group 12.01 +/- .92 cc/min, and continuous group 8.50 +/- 1.45 cc/min. Three weeks of wound healing after microarteriorrhaphy did not significantly change blood flow variables compared to preoperative values.

The present study tests the hypothesis that peripheral hemodynamics in the rat femoral artery remain relatively stable during 3 hours of general anesthesia. Hemodynamic variables (pulse period, maximal centerline velocity, lumen diameter, and mean volumetric flow) were measured by the 20 MHz-pulsed ultrasonic Doppler velocimeter method at 30-minute intervals. The hemodynamic variables were not statistically different during the duration of the study. The mean values were pulse period 160 +/- 2 msec, maximal centerline velocity 37.0 +/- 1.9 cm/sec, lumen diameter 0.94 +/- 0.03 mm, and mean volumetric flow 1.92 +/- 0.19 cc/min.

Interrupted and continuous microsuturing techniques were compared 3 weeks after microarteriorrhaphy in the rat femoral artery using light microscopy, and internal luminal diameter determinations were measured with a Bio Quant II Digitizer. The histologic appearance of the arteries of both groups was similar, with intimal hyperplasia, intimal incorporation of suture projections into the lumen, minimal inflammatory response to suture material, and restoration of the media. No significant difference was demonstrated between internal diameters at the anastomosis site for the continuous (N = 11, mean diameter 804 +/- 60 microns) and interrupted (N = 11, mean diameter 901 +/- 45 microns) groups. However, the experimental arteries in both continuous and interrupted groups were significantly dilated when compared to their controls (513 +/- 41 microns and 621 +/- 44 microns, respectively). This study indicated that interrupted and continuous suture techniques in laboratory microarteriorrhaphy result in similar histologic and morphologic characteristics, and that the repaired vessels were dilated compared to intact vessels.