6-Year Results of CNV Secondary to Pathological Myopia Treated with Ranibizumab.

Background The current standard treatment of choroidal neovascularisation (CNV) secondary to pathological myopia (PM) is intravitreal injection of VEGF antagonists. We now present our 6-year results after treating patients with CNV secondary to PM with ranibizumab. Patients and Methods We retrospectively analysed 15 treatment-naive eyes of 13 patients (10 women, 3 men, mean age 59.2; standard deviation (SD) 11.1; range 41-78 years) with visual impairment related to CNV secondary to PM, who were treated with at least 1 injection of ranibizumab. Follow-up treatments were indicated according to our PRN (pro re nata) regimen. Re-treatment criteria were: reduction in visual acuity and/or activity in OCT or fluorescence angiography. Results Patients received a mean of 3.5 ranibizumab injections (SD 3.4; range 1-12) during a mean follow-up of 85 months (SD 6.6; range 76-102 months). Initial spherical equivalent was - 12.4 ± 4.0 dpt (range - 7.5 to 20.5 dpt). Baseline visual acuity was (log MAR) 0.65 ± 0.28. After one month, visual acuity improved to 0.43 ± 0.23 (p = 0.002), after 3 months to 0.38 ± 0.22 (p = 0.002), after 6 months to 0.34 ± 0.22 (p = 0.002) and after 9 months to 0.35 ± 0.23 (p = 0.002). After 1 year, visual acuity was 0.35 ± 0.24 (p = 0.001), after 2 years 2 0.35 ± 0.23 (p = 0.001), after 3 years 0.35 ± 0.23 (p = 0.002), after 4 years 0.37 ± 0.23 (p = 0.002), after 5 years 0.38 ± 0.23 (p = 0.002), and after 6 years 0.39 ± 0.26 (p = 0.016). Conclusion After considerable initial improvement in visual acuity, the initial gain was maintained by a strict PRN regimen for the observation and treatment of patients with neovascular membranes secondary to pathological myopia. The number of injections needed to achieve stable visual acuity was lower than with other diseases that respond to anti-VEGF.

[Intravitreal anti-VEGF treatment of choroidal neovascularization (CNV) in pathological myopia (PM): a review]. / Intravitreale Anti-VEGF-Behandlung choroidaler Neovaskularisationen (CNV) bei pathologischer Myopie (PM): ein Review.

Anti-VEGF injections are widely used "off-label" for the treatment of choroidal neovascularization secondary to pathological myopia based on data generated by multiple case series with small sample sizes. In this review we have analyzed the results of case series with at least 20 patients and a follow-up of ≥ 12 months. 18 case series were identified in Medline meeting these demands. The mean gain of visual acuity after 12 months was 2.2 ± 0.7 (mean ± 1 standard deviation, case number weighted: 2.0) lines with a mean of 3.0 ± 1.7 injections (case number weighted 2.7). There was no significant difference between bevacizumab and ranibizumab. The mean gain of visual acuity in the first year could be stabilized in the second year with a visual acuity of a mean of 2.2 ± 1.0 lines at the end of follow-up. The mean age of patients at the beginning was 56.0 ± 6.0 (case number weighted: 56.2). The results of this analysis indicate very clearly that a favourable long-term outcome can be achieved with a relatively small number of injections in cases of choroidal neovascularization secondary to pathological myopia.

Three years follow-up results of ranibizumab treatment for choroidal neovascularization secondary to pathologic myopia.

BACKGROUND: Choroidal neovascularization (CNV) secondary to pathological myopia (PM) is one of the main causes of severe visual impairment in patients younger than 50 years. In this analysis we want to demonstrate the long-term results of Ranibizumab treating CNV secondary to PM. PATIENTS AND METHODS: We retrospectively analysed 15 treatment naive eyes of 13 patients (10 women, 3 men, mean age: 61.5, SD 11.6, range: 41-80) with visual impairment due to CNV secondary to PM, which were treated with ranibizumab. Criteria for re-treatment were reduction of visual acuity and/or activity in OCT or fluorescence angiography. RESULTS: We applied a mean of 3 injections (standard deviation [SD] 2.5, range: 1-8) ranibizumab during a mean period of 39.6 months (SD 5.3, range: 31-52). The spherical equivalent was -12.4 diopters ± 4.1 (range -7.5 to -20.5 diopters). Before the first injection mean visual acuity (logMAR) was 0.69 ± 0.26. After one month visual acuity improved to 0.39 ± 0.23 (p = 0.002), after 3 months to 0.30 ± 0.22 (p = 0.002) and after 6 months up to 0.30 ± 0.22 (p = 0.002). After 12 months visual acuity was 0.30 ± 0.22 (p = 0.001) and after 24 months 0.30 ± SD 0.24 (p = 0.001). 11 patients reached a follow-up of at least 36 months and visual acuity was 0.30 ± 0.13 (p = 0.001). CONCLUSIONS: Treating CNV secondary to PM with ranibizumab during a follow-up of 36 months, we found considerable improvement of visual acuity. Compared to treatment of CNV secondary to exudative age-related macular degeneration, CNVs secondary to PM seem to respond faster to ranibizumab treatment and less injections are neccessary to reach stabilization.

[Analysis of choroidal folds of the posterior pole in excessive hyperopia using SD-OCT with enhanced depth imaging (EDI)]. / Darstellung von Aderhautfalten des hinteren Pols bei hoher Hyperopie durch SD- OCT mit verbesserter Tiefenauflösung (EDI).

BACKGROUND: Until now the diagnostic possibilities for choroidal folds were limited to conventional methods like ICG angiography and ultrasound and in many cases additional diagnostic tools like MRI and OCT were necessary. With the introduction of high-resolution OCT new modalities of differential diagnostics are possible. METHODS: During the last year 3 patients with conspicious funduscopic findings were presented in our office. In 2 patients the changes were observed during the pre-operative examinations before cataract surgery, the third patient had problems with reading in the reading distance. After a complete ophthalmic examination we performed measurements of the choroidal complex using a Spectralis OCT (Heidelberg Engineering) with enhanced depth imaging (EDI) and detected choroidal folds in the area of the temporal vessels without hints for impressing changes from outside. Furthermore we performed a photo documentation. RESULTS: Best corrected visual acuity in patient 1 was at the right eye sph + 8.50 cyl -0.75/25° = 0.6 and at the left eye sph + 9.25 cyl -0.75/170° = 0.5. In patient 2 visual acuity was OD 0.6 and OS 0.5 (OD sph + 8.50 cyl -2.25/10° und OS sph + 7.75 cyl -1.25/175°). The anterior ocular segment was normal besides the cataract, the posterior ocular segment showed parallel choroidal folds in the area of the temporal vessels. The choroid was preserved in full thickness and the folds were parallel in the retina and the choroid, without a distance between the two layers. In patient 3 visual acuity was OD/OS 1.0 with a correction of OD/OS sph + 3.75. The posterior ocular segment showed the same choroidal changes, all the other ocular findings were normal. CONCLUSION: Using the SD-OCT with enhanced depth resolution the characteristics of idiopathic choroidal folds in excessive hyperopia can be presented. Our observations can be used for the differentialdiagnostic judgement of idiopathic choroidal folds of the posterior pole.

Heavy internal tamponade for cases with complicated retinal detachment.

PURPOSE: The aim of this review was to compare clinical data on the efficacy and complications of heavier-than-water internal tamponades (F6 H8®, Oxane HD®, Densiron 68®) used in eyes with complicated retinal detachments. METHODS: An analysis was made of all case series with at least 10 eyes treated and cited in Medline together with results of 4 own institutional case series. RESULTS: Short-term internal tamponade with each of the mentioned substances led to successful anatomic results in a relatively high percentage of eyes. The spectrum of complications presented a considerable variation among studies. Data indicate the following trends: F6 H8® was reported to develop emulsification in a relatively high percentage of treated cases and was reported to be related with a high risk of long-term chronic hypotony. Eyes with Oxane HD® presented a relatively high rate of clinically significant inflammatory reactions and secondary membrane formation. Use of Densiron 68® was relatively frequently associated with emulsification. CONCLUSION: The heterogeneity of available clinical data does not allow a definitive comparison of the 3 heavier-than-water endotampondes. The data so far available seem to indicate as a trend that Densiron 68 may provide advantages compared to other substances concerning the relative incidence of severe complications. On the background of relatively high rates of heavy silicone complications it seems reasonable to regard conventional "light" silicones as first choice if a silicone endotamponade is desired and no need for a gravity effect of the endotamponade is indicated.

[Results of ranibizumab treatment for choroidal neovascularization secondary to pathological myopia]. / Ergebnisse der Therapie choroidaler Neovaskularisationen bei pathologischer Myopie mit Ranibizumab.

PURPOSE: Choroidal neovascularization (CNV) secondary to pathological myopia (PM) occurs in up to 10 % of PM and the natural course often leads to a considerable deterioration of visual acuity. Treatment options like laser or PDT can stabilize visual acuity. Alternatives like ranibizumab are new treatment options that show very promising results. It was the aim of this analysis to evaluate the development of visual acuity and the number of injections needed in patients with myopia-associated secondary CNVs. METHODS: We retrospectively analysed 10 eyes of 9 patients (7 women, 2 men, mean age: 66 years, SD 8.3; range: 54 - 78 years) treated with ranibizumab because of CNV secondary to PM. All eyes were treatment naïve. Criteria for re-treatment were loss of visual acuity and/ or activity in OCT or fluorescence angiography. RESULTS: During the mean follow-up of 10 months (SD 6.1; range: 6 to 26 months) a mean of 2.5 (SD 1.6, range: 1 to 5) injections of ranibizumab was applied. The spherical equivalent was - 12 D (SD 4.8, range - 7,5 D to - 20.5 D). Previous to the first injection mean visual acuity was logMAR 0,64 (SD 0.20) (ETDRS: 52.8; SD: 11.4) and during the follow-up a mean of 3.4 lines (ETDRS: 16.5 letters) was gained (p = 0.008). After one month visual acuity improved to log MAR 0.47 (SD 0.1, p = 0.0012) (ETDRS: 61.7; SD: 6.5), after 3 months log MAR 0.38 (SD 0.1, p = 0.012) (ETDRS: 65.8; SD: 5.6) and after 6 months up to log MAR 0.35 (SD 0.1, p = 0.008) (ETDRS 67.3; SD 5.6). At the end of the follow-up visual acuity was log MAR 0.30 (SD 0.1) (ETDRS: 69.3; SD: 6.7).No patient experienced a loss of visual acuity. No ocular or systemic side effects were observed. CONCLUSION: According to our results treatment of CNV secondary to PM with ranibizumab leads to a substantial improvement of visual acuity. It seems that successful treatment of CNV secondary to PM needs less anti-VEGF injections than the treatment of neovascularizations due to age-related macular degeneration. Anti-VEGF seems to be a promising alternative to PDT and laser photocoagulation in myopia-related CNV.

[Focal laser photocoagulation in patients with diabetic macular edema after pretreatment with triamcinolone: 6-month results]. / Fokale Laserkoagulation des diabetischen Makulaödems nach vorbereitender Triamcinolon-Injektion: Ergebnisse nach 6 Monaten.

PURPOSE: The aim of this study was to analyse the 6-months results of focal laser photocoagulation (LC) applied after previous intravitreal injection of triamcinolone in eyes with non-proliferative diabetic retinopathy and clinically significant diabetic macular edema (DME). PATIENTS AND METHODS: 32 eyes (32 patients) with DME were included in this study. The number of laser treatments was: 1 in 14 eyes, 2 in 11, 3 in 4 eyes, 4 in 2 and 5 in 1 eye. The first LC was performed at a median of 17 days (mean: 20.3 +/- 6.5, range: 14 - 42 days) after triamcinolone injection. The second, if necessary, at a median of 32.5 (mean: 45.6 +/- 36.6, range: 22 - 144) days after injection. RESULTS: Mean logMAR visual acuity improved from baseline 0.56 (median: 0.48; 95 %-confidence interval [CI]: 0.41 - 0.71) to 0.47 (median: 0.40, CI: 0.36 - 0.58) after 1 month, and 0.49 (median: 0.40, CI: 0.38 - 0.61) at 3 months, and 0.47 (median: 0.40, CI: 0.36 - 0.58) at 6 months (p < 0.0065). Mean central retinal thickness (OCT-CRT) of optical coherence tomography measurements improved from 417 microm (median: 402.5, CI: 375 - 460 microm) at baseline to 301 microm (median: 280, CI: 271 - 331) at 1 month, 318 microm (median: 305, CI: 276 - 360) at 3 months and 348 microm (median: 329.5, CI: 299 - 398 microm) at 6 months (p = 0.0256). A second combination therapy was performed in 1 eye 3 months after the first injection. In 7 / 32 eyes (22 %) further injections and LC were indicated after 6 months. 8 / 32 eyes received newly prescribed antiglaucomatous medication and 4 / 32 eyes cataract surgery during follow-up. CONCLUSION: Focal LC after previous injection of triamcinolone results in an early and in most cases persistent functional improvement in eyes with DME.

[Intravitreal bevacizumab for recurring choroidal neovascularisation]. / Intravitreales Bevacizumab bei rezidivierender idiopathischer chorioidaler Neovaskularisation.

We administered bevacizumab intravitreally to treat a recurrence of CNV after confocal laser coagulation and photodynamic therapy in a 32-year-old female patient with a single functional eye. Before and after treatment the vision in the affected eye was stable at 1.0. Before administration of the VEGF antibody leakage was distinctly seen on fluorescein angiography, which did not appear on examination after the treatment. Despite the entailed measure of risk we decided in favour of intravitreal application because it seemed promising in view of earlier positive clinical experience with it in exsudative AMD and macular oedema following central retinal vein occlusion. Intravitreal bevacizumab is an alternative that should also be considered for the treatment of idiopathic CNV. Careful clinical studies will follow.

[Diabolic injury with the localization of foreign bodies in the apex of the intraorbital region ]. / Diabolo-Verletzung mit Lokalisation des Fremdkörpers im Bereich der Orbitaspitze-ein Fallbericht.

BACKGROUND: Air-gun injuries with localisation of the pellet at the apex of the orbital cavity can cause difficult decisions in diagnostics and therapy, especially if you decide to retain the foreign body. METHODS: We report on a 14-year-old boy who was hit by an air-gun pellet. The foreign body went into the left orbit without damaging the globe or the optic nerve. RESULTS: The visual acuity was 1.0, the mobility was only slightly disturbed. A systemic therapy with antibiotics and corticosteroids could stop a series of relapses very well. CONCLUSIONS: Foreign bodies of the orbit can be retained if it is possible to deal with the surrounding reactions properly by conservative therapy.

Role of routine nonenhanced head computed tomography scan in excluding orbital, maxillary, or zygomatic fractures secondary to blunt head trauma.

The purpose of this paper is to determine the necessity of a dedicated facial bone/orbital computed tomography (CT) scan for fracture surveillance in patients who have suffered blunt head trauma and whose routine nonenhanced head CT scan is negative. It is based on a retrospective review of 115 patients presenting to the Emergency Department at a level I trauma center after blunt head trauma. Included patients underwent both a nonenhanced head CT scan and a dedicated facial bone or orbit CT. Standard nonenhanced head CT protocol was followed for each patient as per department protocol. A positive head CT scan is defined to include either an air-fluid level within the paranasal sinuses or fracture of the maxillary, orbital, or zygomatic osseous structures. A negative scan demonstrates none of these findings. Intracranial/parenchymal pathology was not evaluated in this study. Sixty-five of the 115 patients had a negative head CT scan as defined above. Of these 65 patients, none subsequently had a positive facial bone or orbit CT scan. The sensitivity and negative predictive values of a negative routine nonenhanced head CT scan for fracture surveillance are both 100%. In the setting of blunt trauma, a negative nonenhanced head CT scan precludes the need for a dedicated facial bone or orbital CT scan in the evaluation for orbital, maxillary, or zygomatic fractures. This saves the patient unnecessary radiation exposure, health care costs, and time spent in the emergency radiology department.

Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury.

BACKGROUND: Acute deterioration of renal function is an important side-effect of angiotensin-converting enzyme (ACE) inhibitors, especially if accompanied by other nephrotoxic events. Angiotensin II receptor(1) blockers (ARB) are thought to have fewer side-effects on renal perfusion and function. We examined the effects of valsartan (VAL) on kidney function as well as the contribution of the nitric oxide (NO) system in a rat model of ischaemic acute renal failure (ARF). METHODS: ARF was induced by 40 min of clamping of both renal arteries in female Sprague-Dawley rats. Renal haemodynamic and tubular parameters were determined during post-ischaemic infusion of vehicle, VAL, VAL and the NO-synthase substrate L-arginine, and VAL together with inhibition of NO synthases (NOS) by L-NMMA. RESULTS: Clamping induced acute renal failure with marked decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) accompanied by a rise in renal vascular resistance (RVR) and fractional sodium excretion. Valsartan caused a slight but significant improvement of GFR and RPF without full recovery of renal function and caused a lowering of RVR and tubular sodium loss. L-arginine-co-administration had no additive beneficial effect. Valsartan-induced changes were not significantly depressed by unspecific inhibition of NOS. CONCLUSIONS: Inhibition of the angiotensin II-receptor(1) diminishes the deleterious effects of ischaemia and reperfusion on glomerular function and on the renal microcirculation. An involvement of the NO system could not be demonstrated.

Estimates of beat to beat handling of activator calcium using measurements of [Ca2+]i in aequorin loaded ferret cardiac muscle.

OBJECTIVE: The aims were (1) to measure simultaneously and on a beat to beat basis intracellular calcium concentration ([Ca2+]i) transients and force transients in isolated ferret cardiac trabeculae; (2) to obtain and compare independent estimates of the recirculating fraction of Ca2+ using the [Ca2+]i data and the force data (recirculating fraction is the fraction of activator Ca2+ taken up by the sarcoplasmic reticulum in each beat and, in the steady state twitch, the fraction of activator Ca2+ released by the sarcoplasmic reticulum); and (3) to estimate the amount of Ca2+ that returns to the sarcoplasmic reticulum and the amount that, during steady state contractions, enters the cytosol, presumably from the extracellular compartment, with each beat. METHODS: Eight trabeculae were mounted in the myograph. The servo-controlled muscle length was 98% of the length at which developed force was maximal. A modified technique was used for chemical loading of aequorin, and a new method for computer controlled low level photon counting, storage, calibration, and analysis. [Ca2+]i transients and force transients were simultaneously recorded during potentiated beats, together with their respective decays toward control steady state [Ca2+]i transients and force transients. A modified test of postextrasystolic potentiation achieved with a brief train of rapid pacing followed by a pause was used to evoke the potentiated beats. RESULTS: At 2.0 mM extracellular Ca2+ ([Ca2+]o), resting [Ca2+]i was 283(SD 77) nM. The resting tension was 1.6(0.3) g.mm-2. The steady state [Ca2+]i transient and the peak potentiated [Ca2+]i transient averaged 992(165) and 1290(154) nM respectively. The corresponding tensions were 4.0(1.9) and 8.7(3.1) g.mm-2 respectively. The recirculating fraction of Ca2+ calculated from the dissipation of the potentiated [Ca2+]i transient averaged 45(4)%. This recirculating fraction was indistinguishable from the one calculated with another method from the decay of the force potentiation. CONCLUSIONS: This is the first study to estimate the recirculating fraction of activator Ca2+ using measurements of [Ca2+]i. The results indicate that over a wide range of [Ca2+]i and tensions the Ca(2+)-force relationship is well approximated by a straight line. At 2.0 mM [Ca2+]o it appears that some 450 nM of Ca2+ recirculates and that a similar amount per steady state beat enters the cytosol, probably from the extracellular compartment.

Beat-to-beat measurements of [Ca2+]i and force in ferret cardiac muscle after chemical loading of aequorin.

This communication reports the development of a modified procedure for chemical loading of aequorin in small multicellular cardiac preparations, with special emphasis directed toward the implementation of a new method for computer-controlled low-photon counting and digital processing and analysis of the data to obtain intracellular Ca2+ concentration ([Ca2+]i). In eight ferret right ventricular trabeculae, we measured the mechanical performance and found that, at 1.25 mM extracellular Ca2+ concentration ([Ca2+]o), resting tension, developed tension, and time to peak tension were unchanged by the loading procedure. Estimated resting and peak systolic [Ca2+]i were 299 +/- 65 and 766 +/- 131 nM, respectively. Thirty minutes after raising the [Ca2+]o to 5 mM, there was a robust increase in mechanical performance, with peak systolic [Ca2+]i averaging 1,218 +/- 222 nM. The diastolic [Ca2+]i remained unchanged. In four other trabeculae, exposure to a low-Na(+)-containing superfusate demonstrated a remarkable beat-to-beat correspondence of increases in diastolic [Ca2+]i and resting tensions. The same beat-to-beat concordance was also observed between the rapidly changing amplitudes of peak [Ca2+]i and developed tension. In additional experiments, simultaneous recordings of [Ca2+]i and force transients were obtained during rapid pace pause maneuvers. These studies showed distinct and quantifiable fluctuations of [Ca2+]i in a 1:1 relation to the mechanical record to a frequency of at approximately 300 beats/min. These results demonstrate that beat-to-beat measurements of [Ca2+]i and tension transients can be obtained with good resolution in multicellular cardiac preparations.

A survey of radiation oncologists regarding their radiation physics instruction.

The American Association of Physicists in Medicine, Committee on Training of Radiologists conducted a survey of radiation oncologists requesting information regarding their radiation oncology physics training. General questions were asked of the oncologist regarding their radiation oncology practice such as number of oncologists, number of new patients treated, and the size and type of facility in which the practice is located. The oncologist also responded to questions regarding their educational background. The survey requested the radiation oncologists to answer questions regarding the adequacy and importance of their training in specific areas of radiation physics. The responders indicated that the importance of most physics topics in their clinical practice corresponded to the level of their understanding. The survey indicated that for most radiation oncologists their physics instruction was an important and interesting part of their residency program.

Dose-response characteristics of a ferrous-sulphate-doped gelatin system for determining radiation absorbed dose distributions by magnetic resonance imaging (Fe MRI).

The nuclear magnetic resonance (NMR) longitudinal relaxation rate R1 dose-response characteristics of a ferrous-sulphate-doped chemical dosimeter system (Fe MRI) immobilized in a gelatin matrix were explored. Samples containing various concentrations of the FeSO4 dosimeter were irradiated to absorbed doses of 0-150 Gy. R1 relaxation rates were determined by imaging the samples at a field strength of 1.5T(1H Lamor frequency of 63.8 MHz). The response of the system was found to be approximately linear up to doses of 50 Gy for all FeSO4 concentrations studied (0.1-2.0 mM). Changing concentrations in the range of 0.1-0.5 mM affected both the slope and intercept of the dose-response curve. For concentrations of 0.5-2.0 mM, the slope of the dose-response curves remained constant at approximately 0.0423 s-1 Gy-1 in the dose range of 0-50 Gy. However, the intercept of the curve continued to increase in that region, as expected, because of the additional paramagnetic ions. The reproducibility of the absorbed dose estimates for measurements made over a 22 cm field of view was found to be 5% in the range of 20-50 Gy (an uncertainty of 0.81 Gy on average), decreasing to approximately 10% in the dose range of 5-10 Gy.

Excitation-contraction coupling model to estimate the recirculating fraction of activator calcium in intact cardiac muscle.

Potentiated contractions were evoked with rapid pace pause maneuver in 14 length-clamped ferret papillary muscles paced 12 times/min at 25 degrees C. At 1.25 mM [Ca2+]o the average steady-state force was 2.94 +/- 1.08 g/mm2 and the potentiated contraction averaged 10.96 +/- 1.61 g/mm2. At 5.0 mM [Ca2+]o the steady-state force increased to 6.18 +/- 1.23 g/mm2 and the potentiated contraction averaged 12.08 +/- 1.15 g/mm2. Under the conditions of these experiments the potentiated contraction obtained at 5.0 mM [Ca2+]o is equal to the maximum twitch tension (Fmax) these muscles can generate. We have previously shown that Fmax is an equivalent of maximal calcium activated force. Since there is a beat to beat nearly exponential decay of the evoked potentiation, the fraction (= fraction x) of the potentiation that is not dissipated with each beat is nearly constant. Using an excitation-contraction coupling model we have previously found that x reflects a measure of the recirculating fraction of activator calcium. Because the tension-calcium relationship is better characterized by a sigmoidal curve, we have now incorporated the Hill equation in the model. To account for the inverse relationship between [Ca2+]i and the magnitude of the slow inward current, a term for negative feedback (h) was also included. We have determined the quantity (x-h) because x and h could not be determined separately. The quantity (x-h) was denoted as x'. The average values of x' at 1.25 and 5.0 mM [Ca2+]o were significantly different (p less than 0.0001), approximately 20% at the lower [Ca2+]o and about 50% at the higher [Ca2+]o.(ABSTRACT TRUNCATED AT 250 WORDS)