Can true monocular keratoconus occur?

Evidence increasingly supports keratoconus as an inherited, genetic disorder. If this is the case, it would be expected to express itself as a binocular condition even though variable expression of the gene may show differing levels in the two eyes. It is a common occurrence in specialist contact lens practices to see pseudo‐monocular keratoconus, that is, an overt clinical level of the condition in one eye and forme fruste keratoconus in the other. The advent of videokeratoscopy has shown almost every case of apparent monocular keratoconus to be different expressions of the condition in the two eyes. Nevertheless, rare cases of the condition are seen that appear to be truly monocular. Such a case is presented in which the condition has been present for more than 23 years. The age of the subject makes the future onset of keratoconus highly unlikely and videokeratoscopy does not show the presence of forme fruste in the ‘good’ eye. There is no history of monocular eye rubbing. Pachymetry shows the normal eye to be well within the range of normal corneal thickness, while the keratoconus in the other eye is sufficiently advanced to warrant corneal grafting. Thus, it is a case of true monocular keratoconus and represents an extreme example of variable gene expression.     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers.

Siberian ginseng ([SG]; Eleutherococcus senticosus) is a commonly used herbal preparation. The objective of this study was to assess in normal volunteers (n = 12) the influence of a standardized SG extract on the activity of cytochrome P450 CYP2D6 and 3A4. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again following treatment with SG (1 x 485 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextorphan were quantified, and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after SG treatment. Likewise, plasma samples were collected (0-60 h) for alprazolam pharmacokinetics at baseline and after SG treatment to assess effects on CYP3A4 activity. Validated high performance liquid chromatography methods were used to quantify all compounds and relevant metabolites. There were no statistically significant differences between pre- and post-SG treatment DMRs indicating a lack of effect on CYP2D6 (P > 0.05). For alprazolam there also were no significant differences in the pharmacokinetic parameters determined by noncompartmental modeling (C(max), T(max), area under the curve, half-life of elimination) indicating that SG does not significantly induce or inhibit CYP3A4 (P > 0.05). Our results indicate that standardized extracts of SG at generally recommended doses for over-the-counter use are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination.     

Abnormal neuromuscular junctions in the lateral rectus muscle of wobbler mice

We have studied the lateral rectus muscles and neuromuscular junctions (NMJs) of abducens motoneurons in wobbler (wr/wr) mutant mice from 26 to 58 days of age. The muscles of wr/wr weighed about 70% of the weight of littermate controls and were composed of fiber types comparable to those of controls, as assayed by succinate dehydrogenase activity. The most obvious difference between wr/wr and control NMJs was a reduction in the length of the postjunctional membrane of wr/wr mice. The mutant muscle endplate membrane was only about 70% (6.58 micron) the length of control muscle regions (9.44 micron). There were no obvious differences at the light microscopic level in the distribution of acetylcholine (ACh) receptors at junctional regions or staining of acetylcholinesterase, as assayed with alpha-bungarotoxin binding or enzyme histochemistry. Indirect immunocytochemical studies using antibodies directed against the subunits of the ACh receptor failed to indicate an abnormal presence of immature receptors clustered at the NMJs of wr/wr mice. Our findings suggest that the formation or maintenance of normal postjunctional folds and the differentiation of receptors at the junctions are under independent control during development. Furthermore, the wobbler mutation may affect muscle cell differentiation as well as neuronal differentiation. This mutant mouse should prove a useful model for study of postjunctional fold formation and function.     

Hypertension, antihypertensive medication and risk of renal carcinoma in California Seventh-Day Adventists

A longitudinal study of 34 198 non-Hispanic white California Seventh-day Adventists identified incident cases of renal carcinoma over six years of follow-up. The use of antihypertensive medications and self-reported hypertension had estimated age-sex adjusted incidence rate ratios of 4.51 and 2.90 respectively. These were relatively unchanged by stratifying on additional variables that may have been confounders. Cases diagnosed later during the follow-up period had the strongest association with hypertension, making the alternative explanation that the cancer may have caused the hypertension less likely. Being married in 1976 (amongst females at least) was also associated with a marked elevation of risk. Point estimates of effect suggested that frequent (greater than or equal to 3 week) consumption of fruit (RR = 0.21) and salad vegetables (RR = 0.34) may be protective for this cancer, although the 95% confidence interval did not quite exclude the null value.     

Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells

In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1β) and tumor necrosis factor-alpha (TNF-α) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1β or TNF-α, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1β or TNF-α, respectively. D54-MG cells require a minimal 1 h exposure to IL-1β in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-α. Simultaneous treatment of D54-MG cells with IL-1β and interferon-gamma (IFN-γ) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-α and IFN-γ. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1β (5.3-fold increase) and TNF-α (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1β and IFN-γ. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-γ, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis.     

Velocity of mammalian skeletal muscle contraction as a function of fiber type, activation, initial length and temperature.

Multiple stepwise regression analyses techniques were applied to develop modifications of the Hill force-velocity equation. Specifically, predictive models of the Hill a coefficient, the Hill b coefficient, and isometric strength P0 were developed for the following set of variables: the fraction of slow-twitch fibers (X), the recruitment magnitude (A), the initial muscle length (L), and the muscle temperature (T). Results indicate that the Hill a and Hill b coefficients and isometric strength P0 can be predicted with a high degree of accuracy. The utility of the equation is that it would allow development of a computer program to control the velocity of contraction of muscles with differing fiber compositions and lengths such as are found in the leg.