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Decalcification of a choroidal osteoma.

A 56-year-old man presented with a clearly defined orange tumour in the posterior pole of his left eye. A choroidal osteoma was suspected, and ultrasonography confirmed the diagnosis. Fluorescein angiography demonstrated subretinal neovascularisation on the nasal edge of the tumour, which was treated with krypton laser photocoagulation twice. Recurrent subretinal neovascularisation occurred one year later and was not amenable to treatment. Three years after the patient first presented, thinning of the tumour was noted on follow-up examination. During the next 15 months the tumour completely disappeared, leaving an area of retinal pigment epithelial and choroidal atrophy. Total decalcification of the choroidal osteoma was demonstrated by ultrasonography.

Calcinosis↗

Photocoagulation of choroidal neovascular membranes with a diode laser.

Nine eyes with parafoveal choroidal neovascular membranes due to age-related macular degeneration or angioid streaks were treated with a diode laser and were followed up to 40 weeks (mean 26 weeks). Angiographically proved closure of the membrane was achieved in seven eyes. Four lesions needed a second treatment for growth of subretinal neovascular tissue. Post-treatment visual acuity ranged from 6/9 to 6/60. Two eyes developed subfoveal membranes resulting in poor visual acuity. The morphology of the diode laser lesions differed from that of the argon green laser and was more similar to that of the krypton laser, producing a 'black hole' on the fluorescein positive print. In one particular eye fluorescein angiography revealed subfoveal choroidal non-perfusion next to the site of the diode lesion suggesting choroidal vascular closure.

Aged↗

Dynamics of phosphorothioate oligonucleotides in normal and laser photocoagulated retina.

AIMS: To investigate the distribution, persistence, and stability of fluorescently labelled phosphorothioate oligonucleotides (PS-ODNs) in normal and laser photocoagulated retina following intravitreal injection in the rat. METHODS: Fluorescently labelled PS-ODNs were injected intravitreally into pigmented eyes at doses of 0.5-10.0 nmol in 2.0 microl solution. The dynamics of PS-ODNs was evaluated by fluorescent microscopy of cryosections and flat mounted retinal pigment epithelium (RPE)-choroid-sclera. Genescan analysis was used to assess the integrity of PS-ODNs in the retina after injection. The dynamics of PS-ODNs was also evaluated in the retina following krypton laser photocoagulation with a protocol producing choroidal neovascularisation (CNV). RESULTS: Following intravitreal injection the PS-ODNs demonstrated dose and time dependent distribution and persistence in the retina, where they accessed all neural layers. However, they preferentially accumulated in the RPE layer, demonstrated as bright granules in the cytoplasm of the cells. Injections of 5.0 and 7.5 nmol of PS-ODNs exhibited strong fluorescence in the retina for 6 weeks after injection. Genescan analysis demonstrated that the PS-ODNs remained almost completely intact for at least 12 weeks. Following laser treatment, the PS-ODNs were concentrated in the regions of laser photocoagulation and retained high intensity for at least 8 weeks after injection, particularly localised to macrophages, RPE, and the local choroidal tissue. CONCLUSIONS: These results indicate that PS-ODNs are stable and accessible to most neural layers of the retina, and they preferentially accumulate in the RPE layer following intravitreal injection. The successful delivery of PS-ODNs into normal and laser photocoagulated retina suggests that PS-ODNs may have potential in the development of therapy for attenuating retinal degenerations and CNV.

Animals↗

Choroidal neovascular membrane inhibition in a laser treated rat model with intraocular sustained release triamcinolone acetonide microimplants.

AIM: To determine if intravitreal microimplants containing triamcinolone acetonide (TAAC) inhibit experimental fibrovascular proliferation (FVP) induced by laser trauma in a rat as a model of choroidal neovascular membranes (CNVMs). METHODS: 20 anaesthetised male Brown Norway rats received a series of eight krypton red laser lesions per eye (647 nm, 0.05 s, 50 micro m, 150 mW). Three types of sterilised TAAC microimplant designs were evaluated: implant A consisting of 8.62% TAAC/20% polyvinyl alcohol (PVA) matrix (by dry weight); implant B consisting of 3.62% TAAC/20% PVA matrix; and implant C consisting of a dual 8.62% TAAC/20% PVA matrix design combined with a central core (0.5 mm) of compressed TAAC to extend the implant release time. For each animal studied, one eye received one of the three aforementioned TAAC implant designs, while the fellow eye received a control implant consisting of PVA but without TAAC. The animals were sacrificed at day 35 and ocular tissues were processed for histological analysis. Serial histological specimens were methodically assessed in a masked fashion to analyse each laser lesion for the presence or absence of FVP; maximum FVP thickness for each lesion was measured from the choriocapillaris. RESULTS: All three types of TAAC implants inhibited FVP relative to controls in a statistically significant fashion. In the eyes that received implant A (n = 8), the mean thickness of the recovered lesions (n = 36) measured 32 (SD 22) micro m, compared to 52 (30) micro m (p <0.005) for the recovered lesions (n = 40) from the fellow control eyes. In the eyes that received implant B (n = 6), the mean thickness of the recovered lesions (n = 31) measured 28 (15) micro m, compared to 50 (29) micro m (p <0.001) for the lesions (n = 19) recovered from the fellow control eyes. In the eyes that received implant C (n = 6), the mean thickness of the recovered lesions (n = 21) measured 39 (24) micro m, compared to 65 (30) micro m (p <0.001) for the lesions (n = 39) recovered from the fellow control eyes. CONCLUSIONS: All three of the tested TAAC microimplant designs produced potent inhibition of FVP in a rat model of CNVMs. There were no differences in inhibition of FVP between the three different types of implants evaluated. This study provides evidence that: (1) corroborates previous investigations that propose TAAC as a potential treatment for CNVMs in humans, and (2) demonstrates TAAC can be effectively delivered via long acting sustained release intraocular microimplants. It should be noted, however, that the FVP observed in this rat laser trauma may not reflect the CNVM observed in human with exudative age related macular degeneration (AMD).

Animals↗

Blood flow and perfusion in acute haemorrhagic pancreatitis in the dog.

Experimental evidence suggests that in acute haemorrhagic pancreatitis in the dog the percentage of the cardiac output distributed to the pancreas falls. Histological evidence indicates arteriovenous shunt flow, but this has not been confirmed by flow measurements. It has recently been reported that in experimental preparations in which pancreatic blood flow is measured through the superior pancreaticoduodenal artery after ligation of other (accessory) vessels, perfusion is reduced in distal regions of the gland. There are no data regarding regional perfusion measurements in acute pancreatitis or the effect of ligating accessory vessels. This study therefore evaluates blood flow and regional perfusion in haemorrhagic pancreatitis in various preparations of the canine pancreas. Perfusion was assessed by measuring the clearance of Krypton-85 after injection into the arterial blood supply of the pancreas. Arterial blood flow was measured by the electromagnetic flow technique. The results show that perfusion in different regions of the gland is similar both before and during disease. If accessory vessels are ligated, however, only perfusion in the head of the gland is maintained. No arteriovenous shunt flow was shown. The percentage of the cardiac output being distributed to the gland did not change in any of the experiments; this contradiction to previous reports may arise from the effective control of acid base balance in this study.

Acute Disease↗

Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats.

BACKGROUND: Recent clinical studies suggest that ischaemic colitis is caused by a microcirculatory disturbance that involves thrombosis of the colon. AIM: To establish a new model of photochemically induced ischaemic colitis in rats. METHODS: Thirty male Wistar rats were anaesthetised with amobarbital, the femoral veins were cannulated and laparotomies were performed. The serosal surface of the proximal colon was irradiated by using a krypton laser (wavelength 568 nm, 20 mW) for four minutes. An intravenous infusion of a photosensitising dye, rose bengal (20 mg/kg body weight), was administered over 90 seconds, beginning at the start of irradiation. Rats were killed immediately (n = 4), 12 hours (n = 2), 24 hours (n = 10), three days (n = 4), seven days (n = 4), 14 days (n = 2), or 28 days (n = 2) after irradiation. Two control rats received laser irradiation without dye infusion. Specimens of the irradiated sites were examined by using histopathology. RESULTS: Localised ulcers of the colon were present in rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features of human ischaemic colitis. Reproducible ulcerative lesions were produced by photothrombosis of microvessels in the colon. CONCLUSION: This model may be useful for further investigation of the pathophysiology of ischaemic colitis.

Animals↗

Right ventricular abnormalities in ventricular tachycardia of right ventricular origin: relation to electrophysiological abnormalities.

Patients with right ventricular tachycardia may have adverse electrophysiological abnormalities linked to disturbed right ventricular structure. Seventeen patients who presented with right ventricular tachycardia without coronary artery disease or gross abnormalities of left ventricular function were studied. Patients had the ventricular tachycardia characterised at electrophysiological study and most underwent radionuclide and contrast angiography. At echocardiography specific attention was paid to the right ventricular chamber size. Two groups were identified at echocardiographic study. In group 1, nine patients had normal left ventricular dimensions and relatively normal features at electrophysiological study. Mean right ventricular ejection fraction was 0.45 by krypton-81 measurement. Group 2 comprised eight patients who had dilatation of right ventricular inflow tract, outflow tract, and right ventricular body. This group had more severe features at presentation and at electrophysiological study. In this group all available echocardiographic measurements of right ventricular chamber size were greater than those of group 1 and outside the normal range. Four of the eight patients in group 2 showed regional right ventricular dyskinesia at echocardiography. Mean right ventricular ejection fraction (0.23) in group 2 was significantly lower than in group 1. One patient in group 2 subsequently died. In patients with right ventricular tachycardia, those with less favourable prognostic features at electrophysiological study may have distinct abnormalities of right ventricular structure that can be identified at echocardiographic study. Echocardiography may be of value in the recognition of potentially malignant clinical and electrophysiological features in this group.

Adult↗

High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer.

BACKGROUND: We investigated the use of high magnification bronchovideoscopy combined with narrow band imaging (NBI) for the detailed examination of angiogenic squamous dysplasia (ASD). This was carried out in relation to bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers at high risk for lung cancer. METHODS: Forty eight patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light and fluorescence bronchoscopic examination was first performed. Observations by high magnification bronchovideoscopy with conventional white light were made primarily at sites of abnormal fluorescence, and then repeated with NBI light to examine microvascular networks in the bronchial mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope system were changed from the conventional RGB broadband filter to the new NBI filter. The wavelength ranges of the new NBI filter were B1: 400-430 nm, B2: 420-470 nm, and G: 560-590 nm. ASD tissues were also examined using a confocal laser scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser sources. RESULTS: The microvessels, vascular networks of various grades, and dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD capillary blood vessels diagnosed by pathological examination. Capillary blood vessels were also clearly visualised by green fluorescence by confocal laser scanning microscopy. There was a significant association between the frequency of dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically (p=0.002). CONCLUSIONS: High magnification bronchovideoscopy combined with NBI was useful in the detection of capillary blood vessels in ASD lesions at sites of abnormal fluorescence. This may enable the discrimination between ASD and another pre-invasive bronchial lesion.

Adult↗

Radiographic, scintigraphic, and gas-dilution estimates of individual lung and lobar volumes in man.

We describe a method of separately determining the volumes of the right and left lungs from conventional chest radiographs and of determining the volumes of individual lobes and pathological spaces, whenever their boundaries are visible radiologically or can be displayed scintigraphically--for example, during fibreoptic bronchoscopy. Scintigrams of individual lungs, lobes, and segments are obtained by deflecting a stream of air marked with 81m krypton down the suction channel of the bronchoscope into the appropriate bronchus during inspiration, followed by a breath-hold during which the image is recorded with a gamma camera. Both radiographic and scintigraphic methods have been validated by comparison with argon dilution estimates of individual lung and lobar volumes also obtained at bronchoscopy, and results for the three methods in normal subjects are presented. Used in conjunction with bronchoscopic soluble gas uptake studies, these volume measurements permit precise estimation of effective perfusion, tissue and water volume, and gas transfer at lobar and segmental level. Individual lung and lobar volumes can be used to quantify lung and lobar collapse and compression, mediastinal shift, regional ventilation and gas trapping, and phrenic paresis.

Adult↗

Use of radionuclide scanning in the preoperative estimation of pulmonary function after pneumonectomy.

Twenty eight patients with bronchial carcinoma were studied before pneumonectomy. Measurement of spirometric indices, static lung volumes, transfer factor (TLCO), and transfer coefficient (KCO) was undertaken before and four months after pneumonectomy. Fourteen of the patients also performed a symptom limited progressive exercise test on a cycle ergometer before and four months after pneumonectomy. All patients had standard xenon-133 ventilation and technetium-99m perfusion scans performed before operation. Eleven patients had krypton-81m ventilation scans in addition. Significant correlations were seen between changes in FEV1, TLCO and KCO and the preoperative function of the resected lung as determined by percentage preoperative perfusion to that lung (p less than 0.001). There were mean decreases in FEV1 of 22% and in vital capacity (VC) of 28.7% predicted. Estimation of postoperative FEV1 from the preoperative values showed equally good agreement with measured postoperative values whether 99mTc perfusion or 81mKr ventilation scans were used in the 11 patients in whom both scans were available. Significant correlations were seen between change in maximum exercise ventilation (VEmax) or maximum oxygen uptake (VO2max) after pneumonectomy and percentage preoperative perfusion to the resected lung (p less than 0.001). Estimation of postoperative maximum ventilation and maximum oxygen uptake from the postoperative values on the basis of 99mTc perfusion scans showed good agreement with observed values. Perfusion scans are useful in estimating not only the changes in spirometric indices that follow pneumonectomy for bronchial carcinoma but also changes in carbon monoxide transfer and exercise capacity.

Adult↗

Pulmonary sequelae in survivors of congenital diaphragmatic hernia.

Nineteen survivors of congenital diaphragmatic hernia repair were compared with age and sex matched control children six to 11 years after repair. All subjects were examined clinically and underwent lung function testing. The patients also had individual lung volumes assessed radiographically and had radionuclide (krypton-81 m, technetium-99 m macroaggregates) ventilation-perfusion (V/Q) lung scans. Four patients had pectus excavatum and two had mild scoliosis. Spirometric measurements were lower in the patients than in the control subjects but only the differences in peak expiratory flow and flow at 50% of expired vital capacity were significant. The radiographic left lung volumes in patients surviving left diaphragmatic repair were larger than expected at 49.3% (SD 2%), suggesting alveolar overdistension. V/Q scans showed a mismatch in the ipsilateral lung, mean Q (40% (7%] being significantly lower than mean V (47% (6%)). In seven patients who had required ventilation for four days or more perfusion to the ipsilateral lung was significantly lower (34% (6%)) than values for the 12 patients ventilated for less than four days (43% (6%)). Survivors of right diaphragmatic repair had a better outcome in terms of relative radiographic lung volumes and V/Q distribution. More severely affected children are now surviving repair of congenital diaphragmatic herniation, with residual pulmonary abnormalities that could produce functional impairment in adult life.

Child↗

Changes in regional ventilation and perfusion of the lung after endoscopic laser treatment.

To determine whether endoscopic laser treatment improves both ventilation and perfusion in patients with advanced lung cancer, krypton-81m ventilation and technetium-99m labelled macro-aggregate perfusion scanning was performed immediately before and two or four days after treatment in a consecutive series of 28 patients. Twelve patients had not received any other treatment before laser therapy and 16 had undergone previous treatments that included radiotherapy. Ventilation and perfusion were quantified by expressing the number of counts in the affected lung as a percentage of the total counts. Ventilation and perfusion improved after laser treatment in 23 patients (82%). The mean ventilation score in the affected lung rose by 50% (p less than 0.001) and the mean perfusion score rose by 24% (p less than 0.001). Incremental changes in ventilation and perfusion scores were positively correlated (r = 0.80). Mean spirometric values, six minute walking distance, the Karnofsky performance index, and breathlessness and wellbeing scores also improved significantly. Patients with main bronchial obstruction who had had no radiotherapy showed the most striking improvements. It is concluded that the removal of intraluminal tumour from the bronchial tree leads to matched improvements in ventilation and perfusion in most patients and that this is associated with valuable improvement in symptoms.

Adult↗

Tc-99m-DTPA aerosol and radioactive gases compared as adjuncts to perfusion scintigraphy in patients with suspected pulmonary embolism.

To evaluate the clinical utility of improved methods for radioaerosol inhalation imaging, we obtained preperfusion radioaerosol images in 107 patients (mean age = 62 years), who were referred for evaluation of suspected pulmonary embolism (PE). For each patient, we compared six-view aerosol images with accompanying perfusion scans and chest radiographs and with Xenon-133 (Xe-133) or Krypton-81m (Kr-81m) studies. Four observers at four different institutions independently evaluated aerosol-perfusion and gas-perfusion pairs, classifying the probability of PE as low, high, or indeterminate. The radioaerosol images were good to excellent in quality; excessive central deposition of activity was infrequent and did not interfere with image interpretation. The aerosol-perfusion studies showed 86% agreement with Xe-133 perfusion interpretations (n = 299) and 80% agreement with Kr-81m perfusion interpretations (n = 99). These rates of agreement were comparable with those of intraobserver agreement for gas-to-gas and aerosol-to-aerosol comparisons, and higher than interobserver agreement rates. In a limited number (n = 9) of angiographically documented cases, aerosol-perfusion and gas-perfusion studies provided accurate and equivalent diagnoses. The results suggest that radioaerosol inhalation studies, performed with improved nebulizers, are diagnostically equivalent to ventilation imaging as an adjunct to perfusion scintigraphy in evaluating patients with suspected PE.

Adult↗

Role of chest radiography in predicting the extent of airway disease in patients with suspected pulmonary embolism.

An independent evaluation of the chest radiographs and ventilation-perfusion (VP) scintigrams of 119 patients (121 studies) was performed to assess the ability of radiographic findings to indicate the extent of ventilation abnormalities in patients suspected of having pulmonary embolism (PE). VP scans were obtained with krypton-81m in 72 cases and with xenon-133 in 49. All scintigrams showing ventilation abnormalities in greater than 50% of the lung were considered indeterminate for PE, owing to an increased likelihood of false-negative interpretations, as reported in previous studies. Indeterminate VP studies were found in all 21 patients who had radiographic findings of widespread obstructive pulmonary disease (OPD), in 35% with radiographic findings of focal OPD (P less than .001), and in only 18% with no OPD seen radiographically (P less than .001). VP scintigraphy is likely to be indeterminate for PE when widespread OPD is seen by chest radiography and ventilation imaging may not be warranted in these patients.

Adult↗

Computed equalization radiography: preliminary clinical evaluation.

Computed Equalization Radiography (CER) was designed to increase visualization of mediastinal structures without affecting lung contrast. CER optimizes the image by obtaining two 1-second fan beam scans. The initial low-dose prescan determines the location of the lungs by means of a stationary krypton gas detector. During the equalization scan, this information is used to position 35 beam attenuators in real time so as to increase exposure of the mediastinum while maintaining ideal optical density over the lungs. Eight observers analyzed 20 pairs of posteroanterior (PA) and lateral radiographs obtained on conventional and CER units. On the PA images, three of four mediastinal areas analyzed were visualized better in CER images, while there was no difference in lung detail. There were no appreciable differences in the lateral projection between the CER and conventional images. Contrast on the PA radiograph was preferred on the CER image. CER provided modest improvement in visualization of mediastinal structures and maintained lung contrast without degrading lung detail on the PA image. CER had no major effect on visualization in the lateral images.

Diagnosis, Computer-Assisted↗

Ventilation-perfusion ratio distributions by mass spectrometry with membrane catheters.

We previously developed a quadrupole mass spectrometer system for measuring gas phase concentrations of multiple inert gases at trace levels. A new inlet with two silicone rubber membrane catheters now allows quantitative analysis of the inert gas concentrations in both blood and gas phase samples. We have determined the sensitivity, linearity, and reproducibility of this system by measuring blood-to-gas phase calibration curves for the following inert gases: sulfur hexafluoride, krypton, Freon 12, enflurane, diethyl ether, and acetone. We have used our mass spectrometer system to obtain multiple inert gas elimination data from three anesthetized, spontaneously breathing dogs. We conclude that our dual-membrane mass spectrometer system provides useful measurements of trace multiple inert gas concentrations in both blood and gas phase samples. Furthermore, the inert gases in blood can be measured directly without having to extract them into a gas phase, and the multiple inert gas elimination data acquired with our system can be used to provide estimates of ventilation-perfusion ratio distributions. Our mass spectrometer technique provides an alternative to the gas chromatographic approach for these measurements.

Anesthesia, General↗

Ventilation-perfusion alterations after smoke inhalation injury in an ovine model.

To study the pathophysiological mechanism of progressive hypoxemia after smoke inhalation injury, alterations in ventilation-perfusion ratio (VA/Q) were studied in an ovine model by using the multiple inert gas elimination technique. Because ethane was detected in expired gas of some sheep, we replaced ethane with krypton, which was a unique application of the multiple inert gas elimination technique when one of the experimental gases is present in the inspirate. Severity-related changes were studied 24 h after injury in control and mild, moderate, and severe inhalation injury groups. Time-related changes were studied in controls and sheep with moderate injury at 6, 12, 24, and 72 h. Arterial PO2 decreased progressively with severity of injury as well as with time. In smoke-exposed animals, blood flow was recruited to low VA/Q compartment (0 < VA/Q < 0.1; 17.6 +/- 10.6% of cardiac output, 24 h, moderate injury) from normal VA/Q compartment (0.1 < VA/Q < 10). However, increases in true shunt (VA/Q = 0; 5.6 +/- 2.5%, 24 h, moderate injury) and dead space were not consistent findings. The VA/Q patterns suggest the primary change in smoke inhalation injury to be a disturbance of ventilation.

Airway Resistance↗

5-Aminolevulinic acid-induced fluorescence endoscopy for the detection of lower urinary tract tumors.

The use of a photodynamic fluorescence marker for diagnosis of tumors is an intriguing concept to improve the thoroughness of surgical tumor resection. Complete surgical resection of multifocal bladder tumors and flat lesions such as carcinoma in situ is known to be difficult, and thus a source of recurrences. We report on the recent experience with the intravesical application of the photosensitizer prodrug 5-aminolevulinic acid (5-ALA), which is a nontoxic physiological heme substrate. Initial results from fluorescence diagnosis using krypton laser light, and recent results with a modified incoherent light source constantly showed a 25% increase in urothelial tumor detection in comparison to white light endoscopy. Due to the high sensitivity, the number of biopsies could be decreased constantly in comparison to routine random biopsies taken under white light endoscopy. The results show about 25-30% of cases with fluorescent lesions which are histologically benign. 5-ALA is a promising tool for the diagnosis of bladder cancer. The outcome of the admission study for 5-ALA in urology in Germany is positive, and is being continued by prospective multicenter clinical studies to prove the hypothesis of reduction of tumor recurrence with this method. 5-ALA-based fluorescence endoscopy is strongly recommended for further clinical testing.

Administration, Intravesical↗