Hypospadias trends in two US surveillance systems

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.     

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.      

The duration of phorbol-inducible ErbB2 tyrosine dephosphorylation parallels that of receptor endocytosis rather than threonine-686 phosphorylation: implications for the physiological role of protein kinase C in growth factor receptor signalling

Tumour cell growth may be accelerated by protein kinase C (PKC) agonists such as phorbol esters and receptor tyrosine kinases, but receptor tyrosine kinases are in turn desensitized to growth factors by PKC agonists. To clarify this apparent PKC bifunctionality, we have used phosphoantibodies to determine the relationship between PKC- dependent phosphorylation events affecting the ErbB2 oncoprotein in G8/DHFR 3T3 cells. Neither the kinetics nor the extent of phorbol- induced juxtamembrane domain (Thr686) phosphorylation vary directly with C-terminal (Tyr1222) dephosphorylation, with Tyr1222 continuing to be dephosphorylated long after Thr686 phosphorylation has also declined. Platelet-derived growth factor (PDGF) mimics the short-term effects of phorbol on Thr686 and Tyr1222 phosphorylation, and confocal microscopy reveals that both of these PKC agonists induce rapid internalization of PKC-modified ErbB2. Phorbol causes sustained cytoplasmic accumulation of PKC-phosphorylated receptors, however, whereas PDGF triggers the appearance of this ErbB2 subset only briefly. Metabolic labelling and co-precipitation studies fail to implicate heterologous molecules in either the tyrosine dephosphorylation or internalization of PKC-modified ErbB2. Taken in the context of earlier juxtamembrane domain mutagenesis studies, these findings indicate that phorbol-activated PKC may desensitize growth factor receptors to extracellular ligands solely by triggering sustained receptor internalization. We submit that PKC-dependent juxtamembrane domain phosphorylation represents a physiological mechanism for shortening the duration and enhancing the specificity of growth factor signalling by promoting internalization of liganded and unliganded receptors, respectively.      

Intracranial chondroma of the occipital lobe

A case report of an intracranial chondroma is discussed with emphasis on magnetic resonance imaging.     

Pseudophakic accommodation with translation lenses – dual optic vs mono optic

PURPOSE: To investigate the pseudophakic accommodation effect in dual and mono optic translation accommodative intraocular lenses (AIOL) using linear matrix methods in the paraxial space. METHODS: Dual (anterior optic of power +32 D linked to a compensatory posterior optic of negative power) and mono lens power was determined in the non-accommodated state using linear geometric optics based on the Gullstrand model eye. The position of the AIOL was calculated from a regression formula. Pseudophakic accommodation was assessed with three systems: (1) forward shift of the mono optic lens, (2) anterior translation of the anterior optic in the dual optic lens system with an unchanged position of the posterior minus lens and (3) symmetrical anterior and posterior translation of the anterior and posterior lens. The Gullstrand model eye was modified by changing the axial length (and proportionally changing the phakic anterior chamber depth) to investigate the accommodative effect in myopic and hyperopic eyes. RESULTS: The dual optic lens system (2) yields a nearly constant accommodation amplitude of 2.4-2.5 D mm(-1) movement over the total range of axial lengths. The mono optic lens (1) provides a higher accommodative effect only in extremely short eyes (high refractive power of the lens), whereas for normal eyes (1.4-1.5 D mm(-1) movement) and for long (myopic) eyes the accommodative effect is much less than the dual optic lens. The dual optic lens system under condition (3) yields less accommodation amplitude compared with the dual optic system under condition (2) over the total range of axial length but provides higher accommodation amplitude compared with the mono optic lens system (1) with axial lengths greater than 22.3 mm (lens power 25.5 D). In the accommodated state, with lens translation of 1 mm, the absolute value of the lateral magnification increases with the refractive power of the mono optic lens (1) and decreases in both dual optic lens systems (under conditions 2 and 3). CONCLUSIONS: A mathematical strategy is presented for calculation of the accommodative effect of mono-optic and dual optic AIOL. The dual optic lens yielded a nearly constant accommodation amplitude of about 2.4-2.5 D mm(-1) translation, whereas the mono optic lens yielded an accommodative response of <2 D mm(-1) translation in long myopic or normal eyes. Only in extremely short eyes is the accommodative amplitude of the mono-optic lens higher than the dual optic lens.     

IL-1α, IL-1β, IL-6, and IL-8 secretion of human keratocytes following photodynamic inactivation (PDI) in vitro

Purpose

With increasing resistance of microorganisms to antibiotics, photodynamic inactivation (PDI) may also be a potential therapeutic option in infectious keratitis. As part of the inflammatory response in infectious keratitis, keratocytes produce various interleukins. The purpose of this study was to evaluate the potential anti-inflammatory effect of PDI, analyzing interleukin-1 alpha (IL-1α), interleukine-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) secretion of human keratocytes following PDI, in vitro.

Methods

Primary human keratocytes were isolated by digestion in collagenase A (1.0 mg/ml) from human corneal buttons, and cultured in DMEM/Ham’s F12 medium supplemented with 10 % FCS. Keratocyte cell cultures underwent illumination using red (670 nm) light for 13 min following exposure to 100 nM concentration of the photosensitizer chlorin e6 (Ce6) in the culture medium. Five and 24 hours after PDI, secretion of IL-1α, IL-1β, IL-6, and IL-8 was measured by enzyme-linked immunoabsorbent assay (ELISA).

Results

The secretion of IL-1α was under the measurement limit in treated and untreated cell cultures 5 and 24 h after PDI. Compared to untreated controls, IL-6 and IL-8 secretion of keratocytes decreased (p?<?0.05 and 0.0001) significantly 5 hours after PDI, whereas IL-1β secretion remained unchanged. Twenty-four hours after PDI, secretion of IL-1β, IL-6, and IL-8 did not differ significantly from untreated controls.

Conclusions

In the short term, PDI does not have an impact on IL-1α and IL-1β secretion of keratocytes, in vitro. Photodynamic inactivation inhibits IL-6 and IL-8 secretion of keratocytes transiently (5 h), which normalizes 24 h following treatment. Through the short-term impact of chlorine e6-PDI on IL-6 and IL-8 secretion, PDI may inhibit the inflammatory cascade in at least keratocyte cultures.     

Biomechanical diagnosis of keratoconus: evaluation of the keratoconus match index and the keratoconus match probability

Purpose:  To evaluate the diagnostic capacity of the Ocular Response Analyser’s keratoconus match index (KMI) and keratoconus match probability (KMP) classification in a sample of keratoconus (KC) patients. Methods: Keratoconus match index and KMP from 114 KC eyes, randomly selected from 114 patients with bilateral keratoconus (KCG), were compared with the corresponding ones from 109 normal eyes (CG). Keratoconus match index’s predictive accuracy was assessed by receiver operating curves (ROC). Keratoconus match probability level of agreement was evaluated at the different KC stages of the Amsler–Krumeich classification. Correlations were estimated with topographic keratoconus classification (TKC), keratoconus index (KI), index of surface variance (ISV), vertical asymmetry (IVA), height asymmetry (IHA), height decentration (IHD), minimal radius (Rmin), central corneal thickness (CCT), thinnest corneal thickness (TCT) mean keratometry (Km) and intraocular pressure (IOPg). Results: Mean KMI in KCG and CG was 0.20 ± 0.38 and 0.98 ± 0.25, respectively (p < 0.01). Significant KMI differences (p < 0.01) were detected in different KC groups [range: 0.62 ± 0.38 (KC 1), ?0.62 ± 0.04 (KC 4)]. Significant correlation was detected between KC staging and KMI (r = ?0.56, p < 0.0001). Keratoconus match probability identified 22.03% of the CG eyes as suspect. Moreover, KMP identified 7.01% and 23.68% of the KCG eyes as normal and suspect, respectively. Receiver operating curves analysis for KMI parameter indicated a predictive accuracy of 97.7% (cut‐off point: 0.512, sensitivity: 91.18%, specificity: 94.34%). Conclusions: Keratoconus match index seems to be a reliable index in keratoconus diagnosis and staging. Keratoconus match probability identifies a significant percentage of topographically defined KC and CG eyes as suspect. Diagnostic capacity of these novel indexes needs to be further explored.     

Biomechanical profile of the cornea in primary congenital glaucoma

Purpose: The aim of our study was to investigate the biomechanical properties of the cornea in primary congenital glaucoma (PCG) and to identify the potential ocular determinants, which affect the corneal biomechanical metrics. Methods: Corneal hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT) were measured in 26 patients with PCG (40 eyes) with the aid of ocular response analyser. In vivo laser‐scanning confocal microscopy was used for the estimation of stromal keratocyte density (KD) and the evaluation of corneal endothelium. Twenty normal subjects (40 eyes) served as controls. Student’s t‐test and Pearson’s correlation coefficients were used for statistical analysis. p Values <0.05 were considered statistically significant. Results: Corneal hysteresis, CRF and CCT were significantly reduced in patients with PCG (all p < 0.05). Corneal hysteresis and CRF negatively correlated with the corneal diameter in both groups (r₁ = ?0.53, r₂ = ?0.66, p < 0.001 for CH and r₁ = ?0.61, r₂ = ?0.69, p < 0.001 for CRF). Moreover, we identified a significant correlation between CH and CRF with CCT in both groups (r₁ = 0.51, r₂ = 0.48, p < 0.001 for CH and r₁ = 0.45, r₂ = 0.44, p < 0.001 for CRF). Mean KD was significantly reduced both in the anterior and posterior corneal stroma in patients with PCG (764 ± 162 and 362 ± 112 cells/mm², respectively) compared with controls (979 ± 208 and 581 ± 131 cells/mm², respectively) (p < 0.001). There was no significant correlation between the keratocyte density in anterior and/or posterior stroma and CH or CRF in any group (r₁ = 0.29, r₂ = 0.31, p < 0.06). Mean endothelial cell density was also significantly reduced in PCG group (2920 ± 443 cells/mm²) compared with control group (3421 ± 360 cells/mm²) (p < 0.001). Pleomorphism and polymegalism were significantly increased in corneal endothelium of patients with PCG. Conclusions: Our results showed a significant reduction in CH and CRF in PCG. Both CH and CRF were negatively correlated with corneal diameter. A significant correlation of CH and CRF with CCT was identified in both groups. Keratocyte density was decreased in PCG, but did not have a significant impact on CH and CRF. Mean endothelial density was also decreased in PCG. Our results suggest that reduced CCT and increased corneal diameter are major ocular determinants for the modified corneal biomechanical profile in PCG, while cellular alterations in corneal stroma and endothelium have no significant biomechanical impact.