Biomarkers in neonates receiving potential nephrotoxic drugs.

OBJECTIVE: Novel biomarkers, such as kidney injury molecule-1 (KIM-1), cystatin, and neutrophil gelatinase-associated lipocalin (NGAL) were shown to predict acute kidney injury (AKI) earlier than serum creatinine in critically ill. We carried out the present study to evaluate these biomarkers in addition to conventional in our neonates. PATIENTS AND METHODS: We recruited 70 neonates of various gestational age groups receiving one or more potential nephrotoxic drug/s. Daily urine samples were collected for estimating KIM-1, cystatin, and NGAL. Modified neonatal kidney disease improving global outcomes (mKDIGO) classification was used in defining AKI. RESULTS: A significant trend in increased urine concentrations of KIM-1, cystatin, and NGAL were observed as we proceed from term to preterm categories. Strong positive correlation was observed between urine albumin and urine albumin creatinine ratio (ACR), and strong negative correlations between urine creatinine and urine cystatin, and between urine creatinine with urine NGAL. A moderate positive correlation was observed between urine KIM-1 and urine cystatin, between urine KIM-1 and urine NGAL, and between urine cystatin and urine NGAL; and a moderate negative correlation was observed between urine creatinine and urine KIM-1. Seven neonates met the mKDIGO criteria for AKI and ROC plot revealed that baseline KIM-1 and NGAL can significantly predict possible drug-induced AKI in neonates. CONCLUSIONS: Urine KIM-1, cystatin, and NGAL are significantly correlated with several other conventional biomarkers that reflect renal function in critically ill neonates. Baseline urine KIM-1 and NGAL concentrations can predict the AKI following potential nephrotoxic drug use in this population.

Atopic profile of asthmatic children in Bahrain.

This study aimed to define the profile of asthmatic children in Bahrain and the prevalence of sensitization to aeroallergens and foods. A total of 95 children who were clinically diagnosed with asthma were enrolled: 71.6% mild, 20.0% moderate and 8.4% severe asthma (NIH criteria). Serum IgE concentrations were elevated (> 200 kU/L) in 21.1% of patients and highly elevated (> 400 kU/L) in 9.5%. Absolute eosinophil counts were elevated (> 350 × 106/L) in 54.8%. Overall, 67.4% of children were atopic; 56.8% were sensitive to inhalant allergens and 39.0% to foods. The atopic profile was generally similar to asthmatic children in the region and worldwide. Conditions significantly associated with atopic asthma included food allergies, allergic rhinitis and eczema.

Atopic profile of asthmatic children in Bahrain

This study aimed to define the profile of asthmatic children in Bahrain and the prevalence of sensitization to aeroallergens and foods. A total of 95 children who were clinically diagnosed with asthma were enrolled: 71.6% mild, 20.0% moderate and 8.4% severe asthma [NIH criteria] Serum IgE concentrations were elevated [> 200 kU/L] in 21.1% of patients and highly elevated [> 400 kU/L] in 9.5%. Absolute eosinophil counts were elevated [>350 X 10[6]/L] in 54.8%. Overall, 67.4% of children were atopic; 56.8% were sensitive to inhalant allergens and 39.0% to foods. The atopic profile was generally similar to asthmatic children in the region and worldwide. Conditions significantly associated with atopic asthma included food allergies, allergic rhinitis and eczema

Uveitis survey in children.

BACKGROUND/AIMS: This is a retrospective cohort uveitis survey to determine the clinical features of uveitis in children and assess the rate of complications at two referral centres in Saudi Arabia. METHODS: All children under the age of 16 years presenting with uveitis for the first time between 1997 and 2007 to The Eye Center and King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia were included. Clinical features of uveitis entities were described. Last follow-up visual acuity and ocular complications were analysed. RESULTS: A total of 163 cases of uveitis in children were included. The age range was 1-16 years with a mean age of 10 years. The most frequent clinical type of uveitis in children included acute anterior non-granulomatous uveitis 26%, intermediate uveitis 20%, Vogt-Koyanagi-Harada (VKH) disease 16% and juvenile idiopathic arthritis (JIA) 15%. Anterior uveitis accounted for 42%, intermediate for 20%, posterior for 7%, and panuveitis for 31%. Immune-mediated uveitis was present in 144 (88%) patients, while infectious causes manifested in 19 (12%) patients. CONCLUSIONS: The most common cause of uveitis in children was anterior non-granulomatous uveitis of undetermined aetiology. There was a high prevalence of intermediate uveitis, VKH and JIA. Infectious causes of uveitis were uncommon.

Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers.

PURPOSE: To evaluate azithromycin tear concentrations after one drop of T1225 0.5%, 1.0%, and 1.5% eyedrops. METHODS: In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5% (n=23), T1225 1.0% (n=38), or T1225 1.5% (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS: T1225 1.0% and 1.5% had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1% at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0% and 1.5% were higher than AUICs of T1225 0.5% and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS: Once daily instillation of T1225 1.0% and 1.5% was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).

Vogt-Koyanagi-Harada associated with diabetes mellitus and celiac disease in a 3-year-old girl.

PURPOSE: To present a case of Vogt-Koyanagi-Harada (VKH) associated with type I diabetes mellitus and celiac disease in a 3 year old female. METHODS: We studied a three-year old female who presented with clinical manifestation of VKH and type I Diabetes mellitus and celiac disease. RESULTS: Patient was found to have hyperglycemia with type I diabetes mellitus. Duodenal mucosal biopsy specimen confirmed the diagnosis of celiac disease. Patient's ocular inflammation was treated by topical and systemic corticosteroid and immune-suppressive therapy. Her diabetes mellitus was controlled by insulin and her celiac disease was controlled by gluten-free diet. CONCLUSIONS: The association of VKH with two autoimmune diseases (celiac disease and type I diabetes mellitus) is rare. This case is, to our knowledge, the youngest patient reported with VKH.

Immunopathogenesis of conjunctival remodelling in vernal keratoconjunctivitis.

PURPOSE: To study the processes involved in mediating conjunctival remodelling in vernal keratoconjunctivitis (VKC) by investigating the expression of integrin receptors, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), transforming growth factor-beta(TGF-beta), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and Ki67 antigen, which is a marker for cell proliferation. METHODS: Conjunctival biopsy specimens from 16 patients with active VKC and nine control subjects were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against the integrin alpha3 and alpha6 subunits, EGFR, VEGF, TGF-beta, bFGF, PDGF, and Ki67 antigen. The phenotype of inflammatory cells expressing growth factors was examined by double immunohistochemistry. RESULTS: In the normal conjunctiva, very weak immunoreactivity was observed for EGFR and VEGF in epithelial cells, and for alpha3 and alpha6 integrin subunits on basal epithelial cells, and on vascular endothelial cells in the upper substantia propria. There was no immunoreactivity for the other antibodies. In VKC specimens, strong staining for alpha3 and alpha6 integrin subunits was observed on the membranes of basal and suprabasal epithelial cells, and all vascular endothelial cells. Immunoreactivity for Ki67 antigen was observed in the nuclei of the basal and suprabasal epithelial cells. Strong immunoreactivity was observed for EGFR in the deeper layers of the epithelium, and for VEGF in all epithelial cells. Inflammatory cells expressing EGFR, VEGF, TGF-beta, bFGF, and PDGF were noted in 8, 9, 11, 10, and 10 specimens, respectively. The majority of inflammatory cells expressing growth factors were eosinophils (45+/-4%) and monocytes/macrophages (35+/-4%). CONCLUSIONS: Chronic conjunctival inflammation in VKC is associated with increased staining of alpha3, and alpha6 integrin subunits, EGFR, VEGF, TGF-beta, bFGF, and PDGF that might mediate conjunctival remodelling.

Clinical and histopathological features of zoonotic cutaneous leishmaniasis in Saudi Arabia.

BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania major is a growing public health problem and endemic in many parts of the Kingdom of Saudi Arabia. The vector is Phlebotomus papatasi and the animal reservoirs are mainly desert rodents. METHODS: In this prospective study, the clinical and histopathological features of ZCL in 120 patients are described and classified. The majority of these patients (n = 84) were non-Saudi expatriate workers who suffered mostly from multiple and severely inflamed nodulo-ulcerative lesions on the exposed parts of the body. Saudi patients were mainly children (n = 21) with few(1-3) lesions on their limbs or sometimes unique erysipeloid facial lesions. RESULTS: Histopathological grouping of ZCL lesions showed four types of granulomatous reactions based on the predominant types of inflammatory cells, presence or absence of necrosis and ranking of parasitic index. CONCLUSION: A possible correlation between histopathologic evolution of ZCL lesions and the immune status of the host is discussed.

Complications of laser in situ keratomileusis (LASIK).

PURPOSE: To report major complications associated with laser in situ keratomileusis (LASIK). METHODS: Twenty-four eyes of 23 patients who underwent LASIK in different centers in Saudi Arabia were included. There were 9 women and 14 men. The age range was from 20 to 65 years. Nineteen of the 23 patients had been referred to the Eye Center for management. All patients had a complete ophthalmologic examination, refraction, corneal topography and pachymetry. RESULTS: The 24 eyes of 23 patients had complications consequent to LASIK. Thirteen were intraoperative complications, and 11 postoperative. Ten (44%) of the 23 cases were related to the corneal flap, two (9%) with intraocular perforation with the microkeratome. Three (13%) had photoablation-related complications. Postoperative complications included three (13%) cases of infections, four (17%) stromal-interface related problems, one (5%) who developed interface vascularization, and one (5%) with non-ischemic central retinal vein occlusion. CONCLUSIONS: Although LASIK is a safe and effective procedure, a small number of patients may suffer serious complications that can even lead to visual loss. The procedure must be carefully performed by qualified surgeons.

Indolent corneal ulcers in a patient with congenital insensitivity to pain with anhidrosis: a case report and literature review.

PURPOSE: To report a case of bilateral corneal neurotrophic ulcer in patient with congenital insensitivity to pain with anhidrosis (CIPA) and review the literature. CASE REPORT: A 6 year-old boy presented with bilateral central corneal sterile ulcer, decreased corneal sensitivity, moderately altered corneal reflex and normal tearing response. History taken, systemic evaluation and medical chart review were undertaken. DISCUSSION: Fifty-two cases of CIPA have been reported worldwide. Fourteen cases had corneal involvement. The clinical picture of our patient is characteristic of CIPA. CONCLUSIONS: Congenital insensitivity to pain with anhidrosis may present as neurotrophic corneal ulcer. We report herewith, this vision threatening corneal congenital abnormality. Early diagnosis and prompt treatment are mandatory to prevent corneal complications such as scarring and perforation.

Laser in situ keratomileusis in eyes with inactive herpetic keratitis.

PURPOSE: To evaluate the safety and outcome of laser in situ keratomileusis in eyes with inactive herpetic keratitis. METHODS: Prospective, interventional case series. In three eyes of three patients with inactive unilateral herpetic keratitis for a minimum period of 1 year, laser in situ keratomileusis was performed. Oral and topical acyclovir were prescribed perioperatively. No topical steroids were prescribed. RESULTS: Preoperatively, all three eyes had corneal stromal scars with induced astigmatism in two eyes and central stromal scar in one eye with best-corrected visual acuity of 20/120, 20/25, and 20/50, respectively. Postoperatively, the three eyes achieved uncorrected visual acuity of 20/20, 20/20, and 20/50, respectively, with decreased corneal scar. None of the patients developed herpetic keratitis reactivation during a minimum follow-up of 6 months. CONCLUSION: Laser in situ keratomileusis was safe and effective in the treatment of refractive errors and corneal scars in three eyes of three patients with inactive herpetic keratitis.

Trachoma: a review.

Trachoma is a leading cause of preventable blindness worldwide. The disease is caused by an intracellular epithelial gram-negative bacterium, Chlamydia trachomatis. The presence of children, overcrowding, and the lack of water in the household are factors that predispose to the transmission of the disease. The disease may remain asymptomatic but some patients many complain of redness, irritation, and ocular discharge. The principal initial clinical manifestation is a follicular conjunctivitis that may lead to conjunctival scarring, entropion, trichiasis, corneal thinning, and ulceration. Some patients develop corneal scars that lead to loss of vision. Despite the remarkable progress in our understanding of Chlamydial infections, the basic mechanisms involved in tissue damage and scarring remain to be elucidated. There are several effective therapeutic modalities for trachoma. Azithromycin oral single dose was found to be safe and effective in children with active trachoma. Conjunctival biopsy specimens obtained from adult patients receiving a single oral dose of azithromycin showed sustained high levels of azithromycin (above MIC of chlamydia) for up to 2 weeks after intake. These prolonged high levels of azithromycin in the conjunctival tissue following a single oral dose makes the drug suitable for the treatment of endemic trachoma.

Toxoplasmosis in a group of glucose-6-phosphate dehydrogenase deficient patients.

OBJECTIVE: This was a retrospective study that aimed at evaluating the relative risk of Toxoplasma infection in patients with glucose-6-phosphate dehydrogenase deficiency as compared to a control group with no glucose-6-phosphate dehydrogenase deficiency. METHODS: Ninety-one blood donor volunteers had serology testing from Toxoplasma gondii and were screened for glucose-6-phosphate dehydrogenase deficiency by a qualitative method using fluorescent spot test. They were all males and their ages ranged from 17 to 52 years. RESULTS: Fifty-three persons (58%) were glucose-6-phosphate dehydrogenase deficient and 38 (42%) were glucose-6-phosphate dehydrogenase normal. In the glucose-6-phosphate dehydrogenase deficient group, 31 (58.5%) had positive titers for Toxoplasma; while in the glucose-6-phosphate dehydrogenase normal group 9 persons (24%) had positive titers for Toxoplasma. The relative risk of infection was 2.5 times more in the glucose-6-phosphate dehydrogenase deficient group, a statistically significant difference with a p value of 0.002. CONCLUSION: Glucose-6-phosphate dehydrogenase deficiency seems to increase the risk for Toxoplasma infection by 2.5 fold probably due to decreased killing effect, of phagocytic cells.

Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.

PURPOSE: To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory condition of unknown cause. METHODS: Diagnostic criteria and nomenclature were subjects of discussion at the First International Workshop on Vogt-Koyanagi-Harada Disease on October 19-21, 1999, at the University of California, Los Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by the workshop participants was charged with drafting revised criteria for Vogt-Koyanagi-Harada disease, based on discussions held during the conference. This article is the consensus committee report. RESULTS: New criteria, taking into account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance for the different ocular findings present in the early and late stages of the disease, were formulated and agreed upon by the committee. These criteria are based on additional knowledge and experience of experts in the field and are believed to reflect disease features more fully than previously published criteria. CONCLUSIONS: The revised definition of Vogt-Koyanagi-Harada disease, with expanded diagnostic criteria, will facilitate performance of studies involving homogeneous populations of patients, at various stages of disease, that address unanswered questions regarding treatment and disease mechanisms.

Laser in situ keratomileusis for the correction of hyperopia from +0.50 to +11.50 diopters with the Keracor 117C laser.

PURPOSE: To evaluate excimer laser in situ keratomileusis (LASIK) for the correction of hyperopia. METHODS: We reviewed retrospectively the medical records of 46 patients treated with LASIK for hyperopia. All patients had a complete ophthalmologic evaluation. The corneal bed was ablated using the Bausch & Lomb Chiron Keracor 117C excimer laser to create a paracentral annular ablation under a nasally hinged 160-microm corneal flap with the Chiron Automatic Corneal Shaper microkeratome. Follow-up was a minimum of 6 months. RESULTS: Eighty eyes of 46 patients (23 males and 23 females) were included. Age ranged from 18 to 65 years (mean, 42 yr). The range of preoperative spherical equivalent refraction was +0.50 to +11.50 D (mean, +3.40 D). Mean postoperative spherical equivalent refraction at 6 months was +0.26 D. Six months after surgery, 35 eyes (44%) achieved uncorrected visual acuity of 20/20 or better and 78 eyes (97.5%) achieved 20/40 or better. Forty-six eyes (58%) had a postoperative spherical equivalent refraction within +/-0.50 D of attempted correction, and 67 eyes (84%) were within +/-1.00 D of attempted correction. When using the Bausch & Lomb Chiron Keracor 117C excimer laser to correct hyperopia, eyes with a spherical equivalent refraction less +2.00 D should be overcorrected by 25%, +2.00 to +4.00 D by 30%, and over +4.00 by 40%. The positive cylinder should be overcorrected by 10%. CONCLUSIONS: LASIK was safe and effective in the treatment of hyperopia from +0.50 to +11.50 D. Regression following LASIK for hyperopia remains a problem. A special nomogram was required to achieve results comparable with those for myopia.

Tear tryptase in vernal keratoconjunctivitis.

OBJECTIVES: To determine the tear level of tryptase (a marker of mast cell activation) in vernal keratoconjunctivitis (VKC) before and after treatment. In addition, eosinophil counts in conjunctival scrapings and ocular surface temperature before and after treatment were studied. PATIENTS AND METHODS: A total of 20 patients, 7 years or older with VKC, were included in this study. Tear samples for tryptase determination were collected before and 2 weeks after treatment with 4% disodium cromoglycate eyedrops and 0.1% fluorometholone eyedrops. In addition, conjunctival scrapings were obtained for microscopic evaluation, and measurement of the ocular surface temperature was performed before and 2 weeks after treatment. One patient was excluded because the patient did not receive topical treatment. Control tear samples were collected from 20 normal control patients for tryptase determination. RESULTS: There were 19 patients with VKC (17 males, 2 females). The age range was 7 to 17 years with a mean age of 9 years. The mean number of eosinophils prior to initiation of therapy was 11.37 eosinophils with a range of 1 to 34 per high-power field. Following treatment, the mean number of eosinophils was 3.42 eosinophils per high-power field with a range of 0 to 11 (P<.01). The mean ocular surface temperature for the right eye before treatment was 35.56 degrees C (range, 34.46 degrees C-36.50 degrees C) and after treatment was 33.53 degrees C (range, 31.13 degrees C-35.40 degrees C). For the left eye, the mean ocular surface temperature before treatment was 35.49 degrees C (range, 34.86 degrees C-36.16 degrees C) and after treatment was 33.88 degrees C (range, 32.40 degrees C-35.53 degrees C). The ocular surface temperature was found to decrease significantly following treatment (P<.001). The levels of tryptase in tears of patients with VKC were determined before and after treatment. The mean level was 16.77 ng/mL (range, <5-115 ng/mL). Following treatment with topical 4% disodium cromoglycate and 0.1% fluorometholone eyedrops, the mean level of tryptase decreased to 7.29 ng/mL (range, <5-44.1 ng/mL) (P<.05). CONCLUSIONS: Patients with severe VKC had high levels of tryptase in tears. Following treatment, the level of tryptase in tears decreased significantly.