Vancomycin loading dose is associated with increased early clinical response without attainment of initial target trough concentration at a steady state in patients with methicillin-resistant Staphylococcus aureus infections.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin therapeutic guidelines suggest a loading dose of 25-30 mg/kg for seriously ill patients. However, high-quality data to guide the use of loading doses are lacking. We aimed to evaluate whether a loading dose (a) achieved a target trough concentration at steady state and (b) improved early clinical response. METHODS: Patients with an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48-72 hours after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci or Enterococcus faecium. RESULTS: There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 and 10.2 µg/mL, P = .54). Proportions of patients achieving 10-20 and 15-20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, a loading dose was associated with increased early clinical response for all infections (adjusted odds ratio [OR]: 4.588, 95% confidence interval [CI]: 1.373-15.330) and MRSA infections (OR: 12.065, 95% CI: 1.821-79.959). Study limitations included no Cmin measurements within 24 hours and the inclusion of less critically ill patients. WHAT IS NEW AND CONCLUSION: A loading dose of 25 mg/kg followed by 15 mg/kg twice daily did not achieve the optimal Cmin at steady state in patients with normal renal function. However, more early clinical responses were obtained with a loading dose compared with traditional dosing, possibly because of a prompt albeit temporary achievement of a more effective concentration.

Bilateral lacrimal caruncle lesions.

A 65-year-old man was referred to our hospital for the treatment of a lesion on the medial lacrimal canthus of both eyes. He had a history of perinuclear anti-neutrophil cytoplasmic antibodies, i.e., pANCA-positive interstitial pneumonia. Orbital magnetic resonance imaging excluded space occupying lesions, and laboratory testing excluded thyroid-related diseases. The masses were excised, and histopathological examinations showed sebaceous gland hyperplasia and inflammatory changes around the gland. In addition, the specimen from the left eye showed a retention cyst possibly caused by an infection. It was also possible that the use of steroid was involved in the development of the lesions. A relationship between the ANCA and the lesions was not completely eliminated.

A long-term follow-up of patients with retinopathy of prematurity treated with photocoagulation and cryotherapy.

To evaluate the refractive characteristics of adults diagnosed with retinopathy of prematurity (ROP) treated with ablation treatment as children, we measured best corrected visual acuity (BCVA, logMAR), spherical equivalent refraction (SER), axial length (AL), lens thickness (LT), anterior chamber depth (ACD) and the corneal curvature radius (CCR) from 46 eyes, 24 patients (15-30 years old) that were diagnosed with ROP. Patients were divided into two groups dependent on the size of the treated retina at the time of ablation treatment; i.e., 360 degrees group (treatment over the whole circumference of the retina; n = 18) and partial group (treatment over part of the retina; n = 28). The study showed that LT was significantly larger (P < 1x10(-4)) and ACD was significantly shorter (P < 1 x 10(-3)) in 360 degrees group (4.26 +/- 0.40 mm and 2.92 +/- 0.48 mm, respectively) than those in partial group (3.71 +/- 0.34 mm and 3.42 +/- 0.26 mm, respectively). However, there were no differences in SER (-6.52 +/- 3.54 diopter vs. -5.95 +/- 4.12 diopter, P = 0.31), AL (23.9 +/- 1.42 mm vs. 25.0 +/- 21.48 mm, P = 0.08) and CCR (7.59 +/- 0.37 mm vs. 7.59 +/- 0.19 mm, P = 0.86). These results indicated that the eyes in the 360 degrees group had larger LTs but did not have extended ALs compared with the partial group.

Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 µg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days.

BACKGROUND: A trough concentration (Cmin) ≥20 µg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target Cmin has not been obtained. Even though the recommended high Cmin of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging. METHODS: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72-96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose. RESULTS: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20-40 µg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥ 20 µg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25-12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥ 20 µg/mL. CONCLUSION: A target Cmin ≥ 20 µg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.

Concentration of vascular endothelial growth factor in aqueous humor of eyes with advanced retinopathy of prematurity before and after intravitreal injection of bevacizumab.

PURPOSE: To determine whether an intravitreal injection of bevacizumab alters the concentration of vascular endothelial growth factor (VEGF) in the aqueous humor of eyes with retinopathy of prematurity. METHODS: Seven Stage 4 and three Stage 5 eyes of eight patients with retinopathy of prematurity were studied. Bevacizumab (0.75 mg/0.03 mL/eye) was injected intravitreally in six eyes of six patients after approval was obtained from the Institutional Review Board of Nagoya University Hospital and an informed consent was signed by the parents. Aqueous humor was collected just before the surgery or before the intravitreal injection of bevacizumab. Aqueous humor was also collected immediately before vitrectomy 4 to 48 days after the injection of bevacizumab. Aqueous humor was also collected from four patients undergoing congenital cataract surgery as controls. The concentration of VEGF was measured by enzyme-linked immunosorbent assay. RESULTS: In the 4 control eyes, the concentration of VEGF in 2 eyes was 156 and 158 pg/mL and was not detectable in the other 2 eyes. The average concentration of VEGF was 1,109 pg/mL in the active Stage 4 eyes and 3,520 pg/mL in the active Stage 5 eyes. After bevacizumab injection, the unbound VEGF concentration was 60, 230, and 290 pg/mL in 3 eyes and not detectable in 1 eye. CONCLUSION: Intravitreal bevacizumab resulted in a marked decrease in the unbound VEGF concentration in eyes with retinopathy of prematurity.

Superior oblique palsy with class III tendon anomaly.

PURPOSE: To describe the clinical findings and surgical results of superior oblique palsy with class III tendon anomaly. DESIGN: Observational case series. METHODS: One hundred and forty-one cases of congenital and idiopathic superior oblique palsy were operated on by one surgeon (M.S.) between September 1, 1995 and August 31, 2007. The superior oblique tendons were explored in 26 cases. Among these, five cases were found to have the distal end of the tendon inserted into the Tenon capsule. Preoperative eye alignment, visual acuity, stereopsis measured with Titmus stereo acuity tests (Stereo Fly SO-001; Stereo Optical Co, Chicago, Illinois, USA), and magnetic resonance imaging findings were collected from the patients' records. Main outcome measures included preoperative eye position, surgical results, and stereoscopic acuity. Stereopsis and the amount of vertical deviation were compared in cases with class I, II, and IV tendon anomalies. RESULTS: A total of eight surgeries were performed on five patients with class III superior oblique tendon anomaly. Three muscles were operated on for each patient. The amount of vertical deviation was not significantly different from other types of tendon anomaly. Patients with class I to III tendon anomalies obtained good stereopsis after strabismus surgery, whereas cases with class IV anomaly achieved only limited stereopsis. The number of surgeries performed was significantly higher in cases with class IV anomaly. CONCLUSIONS: Without careful search of the Tenon capsule, the condition can be misdiagnosed as an absent tendon. Strengthening the superior oblique tendon in the Tenon capsule can improve the alignment significantly.

[A case of panuveitis with optic disc neovascularization associated with juvenile idiopathic arthritis which progressed during a clinical trial of etanercept].

PURPOSE: To report a case of uveitis associated with juvenile idiopathic arthritis that progressed from iritis to panuveitis with disc neovascularization during a clinical trial of etanercept, a tumor necrosis factor a (TNF-alpha) blocker. CASE: A 12-year-old girl with juvenile idiopathic arthritis, which had begun at the age of 1 year 7 months. The patient was enrolled in a clinical trial of etanercept at 11 years of age. The methotrexate which she has been taking was stopped, and prednisolone was decreased gradually from 7 mg. The iritis worsened and progressed to panuveitis with disc neovascularization when the prednisolone dose had been tapered to 2 mg. The uveitis was controlled by treatment with a steroid pulse and a liposteroid. CONCLUSION: When starting etanercept therapy in a patient with juvenile idiopathic arthritis who has uveitis and the antirheumatic drug is stopped and steroid treatment tapered, special care is needed to avoid the exacerbation of uveitis.

Development of stereoscopic acuity: longitudinal study using a computer-based random-dot stereo test.

PURPOSE: To investigate the development of stereoscopic acuity (stereoacuity) in children longitudinally. METHODS: Seven full-term normal infants whose age at the beginning of the study was between 12 and 23 weeks were studied. A computer-based random-dot test of stereoscopic vision (TV-Random Dot Stereo Test) was used to measure stereoacuity. The test was repeated at 2- to 3-month intervals until the children reached 2 years of age, and then every 6 to 12 months until they reached 5 years of age. RESULTS: All of the infants were found to have a stereoacuity of 2480 seconds of arc (2480'') with this test by 26 weeks of age. The first reliable measurement of stereoacuity was obtained from a 16-week-old infant. Stereoacuity did not improve significantly between 6 and 12 months, but it improved rapidly after 12 months. All children had a stereoacuity of 100'' with the Titmus Stereo Tests at 5 years of age, but the best stereoacuity with the TV-Random Dot Stereo Test was 229'' at 28.9 months. CONCLUSIONS: The development of stereoacuity studied longitudinally was similar to that obtained by cross-sectional studies. The TV-Random Dot Stereo Test is a useful program for measuring stereopsis in preverbal children.

Similar etiologies of functional visual loss observed in children and adults.

BACKGROUND AND PURPOSE: To describe four cases of functional visual loss which challenge the theory that its causes are different in children and adults (i.e., that financial gain is the primary cause in adults while in children it is an involuntary response to psychosocial problems). Rather, we will show a similar etiology of functional visual loss in children and adults. We also describe diagnostic testing and therapeutic approaches that are useful in both children and adults with functional visual loss. SUBJECTS AND METHODS: Two children (5 and 15 years old) and two adults (54 and 73 years old) with presumed functional visual loss and whose visual functions were assessed with verbal assurance, Starlight Test, Flicker Test, and trial glasses or contact lenses. RESULTS: Normal visual function was elicited in all four cases. In both pediatric patients we were able to elicit normal vision using verbal assurance and trial glasses or contact lenses. In both adult patients, we elicited dramatic improvements in vision with verbal assurance and discussion of the patients' psychosocial situation. CONCLUSION: Children and adults present with similar etiologies (psychosocial problems) of functional visual loss. In these cases we believe the children were motivated by their desire to wear glasses or contacts and the adults were involuntarily responding to psychosocial problems. These cases show that we cannot, as has been proposed, clearly categorize patients with functional visual loss based upon age.

Bagolini striated glasses test and lesions of the optic chiasm.

PURPOSE: To examine the usefulness of the Bagolini Striated Glasses Test to identify patients with a lesion of the optic chiasm. SUBJECTS AND METHODS: Twelve patients who were diagnosed with a lesion of the optic chiasm by MRI were examined with the Bagolini Striated Glasses Test. Discrepancies of the test between monocular and binocular conditions were analyzed. Visual acuity, visual field and stereo tests were also administered and assessed. RESULTS: Nine out of 12 cases (75%) showed conflicting results with the Bagolini Striated Glasses Test between monocular and binocular conditions. With monocular testing, essentially normal stripes were observed in each eye. In binocular testing, stripes which were projected upon nasal retina were suppressed bilaterally (bitemporal hemianopia pattern) ("mountain pattern") or monocularly (monocular temporal hemianopia pattern). CONCLUSION: The Bagolini Striated Glasses Test can be used as a simple differential diagnostic test for lesions of the optic chiasm. The "mountain pattern" seen binocularly on this test may be pathognomonic for such lesions, which may otherwise be asymptomatic and/or overlooked.

Surgical correction of caruncular distortion after medial rectus resection.

Strabismus surgery can lead to successful eye alignment but may cause scarring and distortion of conjunctiva and adjacent structures in some cases. We report two patients who developed epiphora when the lacrimal caruncles became distorted after strabismus surgery. Both cases followed successful medial rectus muscle resections for exotropia. A simple excision of the caruncles improved the epiphora and produced a satisfactory appearance.

Morphological study of acute zonal occult outer retinopathy (AZOOR) by multiplanar optical coherence tomography.

PURPOSE: We set out to determine whether morphological retinal changes occur in patients with acute zonal occult outer retinopathy (AZOOR). METHODS: Five patients diagnosed with AZOOR were studied. They included two men and three women, with an age range of 23-51 years. Symptoms and findings were retrospectively and prospectively collected. The three-dimensional multiplanar optical coherence tomography (OCT) Ophthalmoscope was used to examine the morphology of the retina in patients who were examined between April 2000 to December 2004. Standardized full-field electroretinograms (ERGs) and multifocal ERGs (mfERGs) were recorded. RESULTS: All the patients reported an acute onset of visual disturbances including a decrease of central vision and photopsia. The a- and b-waves of full-field ERGs were decreased, and the mfERGs in the central area were reduced. Ophthalmoscopic examination showed no obvious fundus abnormalities. OCT Ophthalmoscopic images of a cross-sectional plane revealed hyporeflection at the level of the photoreceptor layer in the macular region in three of five patients, and presence of one or two layers in which the inner/outer segment junction of the photoreceptor layer was absent in the other two patients. En-face, constant depth C-scans, which present the image parallel to the retina, revealed an abnormal, patchy hyper-reflection in the affected eyes of two patients and in the non-affected eye in one of these two patients. CONCLUSIONS: The changes in OCT Ophthalmoscope B-scan images indicate morphological damage to the photoreceptors, which probably accounts for the functional alterations. The alterations in the C-scan image in the normal fellow eye of one patient suggest that morphological changes may precede symptomatic changes.

Two types of non-selective cation channel opened by muscarinic stimulation with carbachol in bovine ciliary muscle cells.

In the ciliary muscle, the tonic contraction requires a sustained influx of Ca2+ through the cell membrane. However, little has hitherto been known about the route(s) of Ca2+ influx in this tissue that lacks voltage-gated Ca2+ channels. To identify ion channels as the Ca2+ entry pathway we studied the effects of carbachol (CCh) on freshly isolated bovine ciliary muscle cells by whole-cell voltage clamp. Experiments were carried out using pipettes filled with K+ -free solution containing 100 mm caesium aspartate, 5 mm BAPTA and 180 microm GTP (pH 7.0; the intracellular free Ca2+ concentration, [Ca2+]i = 70 nm). CCh evoked an inward current showing polarity reversal at a holding potential near 0 mV. Analysis of the current noise distinguished two types of non-selective cation channel (NSCCL and NSCCS) with widely different unitary conductances (35 pS and 100 fS). The ratios of the permeabilities to Li+, Na+, Cs+, Mg2+, Ca2+, Sr2+ and Ba2+, estimated by cation replacement procedures, were 0.9: 1.0: 1.5: 0.2: 0.3: 0.4: 0.5 for NSCCL, and 1.0: 1.0: 1.8: 2.5: 2.6: 3.2: 5.0 for NSCCS. NSCCS, but not NSCCL, was strongly inhibited by elevation of [Ca2+]i. Both NSCCL and NSCCS were dose-dependently inhibited by 1-100 microm SKF96365, La3+ and Gd3+, which also inhibited the tonic component of the contraction produced in muscle bundles by CCh without markedly affecting the initial phasic component. NSCCL and/or NSCCS may serve as a major Ca2+ entry pathway required for sustained contraction of the bovine ciliary muscle. RT-PCR experiments in the bovine ciliary muscle (whole tissue) detected mRNAs of several transient receptor potential (TRP) channel homologues (TRPC1, TRPC3, TRPC4 and TRPC6), which are now regarded as possible molecular candidates for receptor-operated cation channels.