Accommodation response and spherical aberration during orthokeratology.

PURPOSE: To evaluate the changes in the accommodative response and in the corneal and internal spherical aberration during 3 months of wear of orthokeratology lenses from the baseline. METHODS: Fifty children aged 8 to 17 were recruited for a prospective study and were fitted with orthokeratology lenses. Refraction without cycloplegia, high and low uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), accommodation lag, horizontal near phoria without correction, corneal topography, corneal, and total wavefront aberration were performed at baseline, 1 day, 1 week, 1 month, and 3 months. Data were analyzed by Student's t test for related samples, repeated measures ANOVA test, and Pearson correlation test. RESULTS: The spherical equivalent (SE) before and after 3 months was - 3.33 ± 1.60 D and - 0.30 ± 0.46 D, respectively. Accommodation lag was 0.53 ± 0.38 D and 0.20 ± 0.33 D at baseline and at 3 months, respectively. A moderate correlation between lag at the baseline and its change between baseline and the 3-month visit was found (P < 0.05; R = 0.748). The spherical aberration (SA) increased for anterior corneal and total measurement, being statistically significant for all visits (P < 0.05). The internal SA decreased: - 0.105 ± 0.006 at baseline and - 0.196 ± 0.203 at 1 week (P < 0.05). No difference between baseline and the follow-up visits in posterior corneal SA was found (P > 0.05) CONCLUSION: The negative SA of the lens increases during OK treatment compensated for the increase of the anterior corneal surface positive SA, in addition to increasing the accommodative response.

The Topographical Effect of Optical Zone Diameter in Orthokeratology Contact Lenses in High Myopes.

PURPOSE: To evaluate the effect of the optical zone diameter (OZ) in orthokeratology contact lenses regarding the topographical profile in patients with high myopia (-4.00 D to -7.00 D) and to study its effect over the visual quality. MATERIALS AND METHODS: Twelve patients (18 eyes) were fitted with overnight orthokeratology (OrthoK) with a randomized 6 mm or 5 mm OZ lens worn for 2 weeks, followed by a 2-week washout period, between both designs. Keratometry (K) readings, optical zone treatment diameter (OZT), peripheral ring width (PRW), higher-order aberrations (HOA), high (HC) and low contrast (LC) visual acuity, and subjective vision and comfort were measured at baseline and after 2 weeks of OrthoK lens wear of each contact lens. RESULTS: No significant differences were found between any measurements for the same subject at both baselines (p value > 0.05). There was no difference between OZ lens designs found in refraction, subjective vision or comfort, and HC and LC visual acuity. Contrast sensitivity was decreased in the 5 mm OZ lens design compared with 6 mm OZ design (p-value < 0.05). 5 mm OZ design provoked a greater flattening, more powerful midperipheral ring and 4th-order corneal and total spherical aberration than the 6 mm OZ design, being statistically significant after 7 days, for corneal aberration, and 15 days, for corneal and total, of wearing the lens (p-value < 0.05). The OZT obtained were 2.8 ± 0.2 mm and 3.1 ± 0.1 mm for 5 mm and 6 mm OZ design, respectively (p-value < 0.05). Regarding PRW, the 5 mm OZ design had a wider ring width in both the nasal and temporal zones (p-value < 0.05). CONCLUSIONS: A smaller diameter optical zone (5 mm) in orthokeratology lenses produces a smaller treatment area and a larger and more powerful midperipheral ring, increasing the 4th-order spherical aberration that affects only the contrast sensitivity but without differences in visual acuity and subjective vision compared with a larger OZ diameter (6 mm).

Primary sclerosing cholangitis in children: a histologic follow-up study.

Primary sclerosing cholangitis (PSC) is rare in the pediatric population. Little information exists on the progression of the disease in children. This study evaluated the experience with PSC at the Children's Hospital of Philadelphia over the past 20 years, with an emphasis on the histologic features at presentation, during disease progression, and after liver transplantation. We retrospectively reviewed the medical records of patients diagnosed with PSC between 1981 and 2001. Nineteen patients met the inclusion criteria with classic radiographic evidence of PSC. One additional patient with normal biliary imaging was subsequently diagnosed at the time of liver transplantation. The 20 patients with PSC (14 males) ranged in age from 1 month to 15 years at time of presentation. Inflammatory bowel disease was evident in 50% of patients. Initial histology revealed advanced disease (bridging fibrosis or cirrhosis) in 13 patients and an earlier histologic stage in 7 patients. Of the latter, 3 remain stable, 2 required transplantation, and 2 were lost to follow-up. Seven of the 13 patients with advanced disease required orthotopic liver transplantation, and 3 of these subsequently showed recurrence of primary disease in the allograft. Thus, most subjects presented insidiously at an advanced stage that required transplantation. Subjects who presented at an earlier stage progressed or remained stable, but the histologic findings at diagnosis were generally not predictive of disease progression. Recurrence of PSC after transplantation is a significant complication in children.

Prokinetic drug therapy in children: a review of current options.

OBJECTIVE: To review the pharmacology, safety, and efficacy of the prokinetic agents metoclopramide and erythromycin in children. DATA SOURCES: English-language literature was accessed using MEDLINE (1970-June 2004) with metoclopramide, erythromycin, macrolides, gastroesophageal reflux, and gastrointestinal motility as the search terms. STUDY SELECTION AND DATA EXTRACTION: Abstracts and original research articles were included. Preference was given to published controlled trials. Articles providing descriptions of pharmacology, safety, and effectiveness of metoclopramide and erythromycin for the treatment of gastroesophageal reflux (GER) were also used in this review. DATA SYNTHESIS: Some authors advocate using a prokinetic agent along with acid suppression for treatment of GER in children. The 2 prokinetic agents most commonly used are erythromycin and metoclopramide. Erythromycin has numerous observational reports and controlled trials demonstrating its efficacy in improving feeding tolerance in children. Adverse drug reactions associated with its use were uncommon in prospective controlled trials. Few data support the use of metoclopramide for management of GER, and the potential adverse effects associated with its use need to be considered before prescribing. CONCLUSIONS: The literature supports the use of erythromycin as a prokinetic agent. Many children with GER are adequately controlled with acid suppression alone; however, if use of a prokinetic agent is warranted, erythromycin in combination with acid suppression should be considered. Given the lack of prospective controlled studies demonstrating metoclopramide's efficacy and safety in the treatment of GER in children, metoclopramide should not be considered a treatment option.

Terminal ileum intubation in pediatric colonoscopy and diagnostic value of conventional small bowel contrast radiography in pediatric inflammatory bowel disease.

BACKGROUND: Small bowel contrast radiography is often suggested as the first diagnostic tool in evaluating pediatric inflammatory bowel disease. The purpose of this study was to determine the sensitivity and specificity of small bowel radiography compared with terminal ileal biopsies in diagnosing pediatric inflammatory bowel disease, and to determine the success rate and safety of terminal ileum intubation during pediatric colonoscopy. METHODS: We retrospectively reviewed the records of 164 subjects who had colonoscopies with terminal ileal biopsies between 1994 and 1996. Small bowel contrast radiography was performed in 84 subjects within two weeks of the colonoscopy. We also reviewed all the colonoscopy reports from the years 1994 to 1996 and 1999 to 2000 to determine the percentage of terminal ileal intubation. RESULTS: Eighty-four subjects with small bowel contrast radiography and terminal ileal biopsies were reviewed. Using small bowel radiography as a screening test for the diagnosis of terminal ileum inflammatory bowel disease resulted in a sensitivity of 45% (17/37) and a specificity of 96% (17/19). Between the years 1994 and 1996 the percentage of pediatric colonoscopies that resulted in terminal ileal intubation was 21.5%; between the years 1999 and 2000 the percentage increased to 65.6%. CONCLUSIONS: A normal small bowel radiography alone should not be used to rule out pediatric inflammatory bowel disease when the symptoms suggest it. Colonoscopy with terminal ileal intubation is feasible and safe; it should be attempted in all children with symptoms consistent with inflammatory bowel disease.

Growth failure in the child with inflammatory bowel disease.

Once considered rare in pediatric practice, chronic inflammatory bowel disease (IBD) is now being recognized with increasing frequency in children of all ages. In IBD, growth failure may be the only clinical presentation; it is imperative to perform a detailed history and physical examination to search for other systemic and gastrointestinal manifestations of the disease. IBD can have a significant impact on linear growth, weight gain, and bone mineralization, and can cause delays in the onset of puberty. Delays in growth and sexual development can be early indicators of disease activity, and assessment of growth and development should be performed frequently. Nutritional therapy is important not only to correct undernutrition, but also as therapy for IBD. Delayed puberty can have a significant impact on the self-esteem of the adolescent patient and diminish final adult height. Loss of bone mineral density is especially significant during a period in which the majority of bone accretion is expected to occur. These issues present unique problems to the gastroenterologist caring for a child or adolescent with IBD and require specific types of monitoring and interventions.

Second primary tumors in patients with cutaneous malignant melanoma.

BACKGROUND: Several studies report coexistent or subsequent primary tumors (SPT) among patients with malignant melanoma (MM), with the rate of incidence ranging from 1.5-20% depending on the sample size and the length and completeness of follow-up. METHODS: The authors followed a cohort of patients with cutaneous MM who were diagnosed and treated at the City of Hope National Medical Center to determine the incidence rate of SPT and associated risk factors. Five hundred eighty-five patients (median age at diagnosis, 43 years) were diagnosed and treated for MM between 1952 and 1996 and followed for a median of 6.5 years (range, 0.0-37.0 years). Ninety-six percent of the cohort had been treated by surgery alone. RESULTS: Thirty-seven patients developed an SPT. These included skin cancers (n = 23), carcinoma of the urinary bladder, breast carcinoma, and lymphoma (n = 3 each), lung carcinoma and prostate carcinoma (n = 2 each), and cervical carcinoma (n = 1). The estimated cumulative rate of incidence after MM was 5% at 5 years for any SPT, 3.7% for a second skin cancer, and 1.1% for a second solid tumor. Overall, the current cohort of MM patients was found to be at an increased risk for developing a subsequent melanoma (standardized incidence ratio [SIR], 4.5; 95% confidence interval [95% CI], 1.2-10.0) when compared with the general population. Older men (age > 50 years at the time of diagnosis of MM) were at an increased risk of developing subsequent bladder carcinoma (SIR, 6.4; 95% CI, 1.2-15.7). CONCLUSIONS: Patients diagnosed with MM are at an increased risk of developing subsequent MM and bladder carcinoma. Issues to be addressed in future studies include interactions between environmental exposures and genetic susceptibility and the identification of individuals at increased risk.

The El Paso smelter 20 years later: residual impact on Mexican children.

Although there has been considerable concern regarding cross-border industrial contamination between Mexico and the United States, there are remarkably few data. One notable case study is the smelter in El Paso, Texas. In 1974 blood lead levels higher than 40 micrograms/dl were detected in 52% of children studied near the smelter, in the adjacent Mexican community of Anapra in Ciudad Juarez, Chihuahua. Lead smelting at this plant was halted in 1985, and as a result, lead levels in air decreased sharply; consequently, children's exposure to lead and other metals should have diminished accordingly. In order to assess the effect of removal of lead emissions from the area, three geographical locations in Anapra, varying in distance from the smelter source, were evaluated for lead, arsenic, and cadmium levels in soil and for lead in blood of children. It was found that lead levels in soil were inversely correlated with distance from the smelter. Arsenic and cadmium levels in soil were constant among the three sectors. However, at residential sites closer to the smelter, a higher percentage of children was found with blood lead levels exceeding the Centers for Disease Control's action level of 10.0 micrograms/dl. In the sector closest to the border 43% of children had blood lead levels greater than 10.0 micrograms/dl. Although blood lead levels in children living in Anapra have dropped approximately fourfold in 20 years, our results indicate a moderate continued risk of lead exposure. This study demonstrates the persistent impact that may result from cross-border contamination and raises provocative questions regarding appropriate action and the responsibility for financing such action.

Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of glutathione levels.

The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels, but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart.

Toxicological assessment of azarcon, a lead salt used as a folk remedy in Mexico. I. Oral toxicity in rats.

Azarcon, a lead tetroxide salt, is used among Mexican and Mexican-American populations for the treatment of digestive illness. Chemical analysis of the azarcon sample used in this study showed it to be 96% lead, 1% calcium, 1% other minor metals, and 2% unidentified material. Taking into account the fact that Pb absorption was estimated at 2% following a single oral administration of 100 mg/kg (Aungst et al., 1981), it is possible to propose a chemical interaction between the components of azarcon, and as a result, the toxicity of Pb tetroxide would be different when given as azarcon than when given as a pure compound. The present work studied this possibility, with the following results. When the treatments of equal doses of pure Pb tetroxide and azarcon were compared (158 mg/kg/day p.o. for 96 h), five of nine tissues studied had similar Pb concentrations. However, with the pure compound the Pb levels were higher in bone and intestines; while with azarcon the Pb levels were higher in heart and brain. The pure Pb tetroxide treatment affects lipid peroxidation only in liver, but a low induction of peroxidation was found also in kidney and heart in rats which received the azarcon treatment. Liver and kidney damage were evident in rats treated with a high dose of azarcon (1.1 g/kg/day p.o. for 96 h), while the effects with the pure compound were similar in type but lower in magnitude. Pb tetroxide as a pure compound inhibits ALA-D by 26% while an inhibition of 42% was found with azarcon.(ABSTRACT TRUNCATED AT 250 WORDS)

Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosí, Mexico.

The main purpose of this study was to assess environmental contamination by arsenic and cadmium in a smelter community (San Luis Potosí City, México) and its possible contribution to an increased body burden of these elements in children. Arsenic and cadmium were found in the environment (air, soil, and household dust, and tap water) as well as in the urine and hair from children. The study was undertaken in three zones: Morales, an urban area close to the smelter complex; Graciano, an urban area 7 km away from the complex; and Mexquitic, a small rural town 25 km away. The environmental study showed that Morales is the most contaminated of the zones studied. The range of arsenic levels in soil (117-1396 ppm), dust (515-2625 ppm), and air (0.13-1.45 micrograms/m3) in the exposed area (Morales) was higher than those in the control areas. Cadmium concentrations were also higher in Morales. Estimates of the arsenic ingestion rate in Morales (1.0-19.8 micrograms/kg/day) were equal to or higher than the reference dose of 1 microgram/kg/day calculated by the Environmental Protection Agency. The range of arsenic levels in urine (69-594 micrograms/g creatinine) and hair (1.4-57.3 micrograms/g) and that of cadmium in hair (0.25-3.5 micrograms/g) indicated that environmental exposure has resulted in an increased body burden of these elements in children, suggesting that children living in Morales are at high risk of suffering adverse health effects if exposure continues.

Arsenic-cadmium interaction in rats: toxic effects in the heart and tissue metal shifts.

Previously, we had shown that arsenic interacts with cadmium in rats; our results showed that the toxicity of a mixture of arsenic + cadmium cannot be predicted by the toxic mechanisms of the individual components. In this paper, we present further evidence about the interaction of arsenic and cadmium in rats. The results were: arsenic modified the 24 h-LD50 value of cadmium more clearly than cadmium did with the one of arsenic; based on the LD50 values, the mixtures we studied were more toxic than either metal alone. With single doses (As 10 mg/kg, Cd 2.6 mg/kg, and As 10 mg/kg + Cd 2.6 mg/kg) the mixture As + Cd was more toxic than each metal. At these doses, cadmium significantly induces the levels of glutathione, metallothionein, and lipid peroxidation in heart tissue, as compared to a saline group of rats. Arsenic incremented glutathione and lipid peroxidation at higher values than those obtained with cadmium. The mixture of As + Cd behaved as arsenic in the induction of lipid peroxidation and glutathione and like cadmium in metallothionein induction. Finally, rats treated with As + Cd had less Cd in liver than animals treated only with cadmium, and more As in heart tissue than rats treated only with arsenic. Our results give further evidence about the arsenic-cadmium interaction in rats, demonstrate the utility of employing different biomarkers in the study of chemical mixtures and indicate that heart tissue is affected not only by the mixture of As + Cd, but also by either metal alone.