Scintigraphic assessment of an ophthalmic gelling vehicle in man and rabbit

Studies of the rate of clearance of a gellan gum formulation (Gelrite) radiolabelled by the inclusion of technetium-99m labelled diethylenetriaminepentaacetic acid were carried out in volunteer subjects and in rabbits. Disposition was followed by gamma scintigraphy and compared with 0.5% w/v hydroxyethylcellulose (HEC) solution and isotonic saline administered to the same subjects. Clearance of all solutions was found to follow bi-exponential kinetics with differences in clearance rates between the two species studied. A significant retention of the gellan gum formulation compared to HEC (p = 0.006) or saline (p = 0.009) was noted in man, but not in the rabbit. In this latter species the HEC showed greater retention compared to Gelrite. The species-specific differences in the precorneal residence of the formulations are attributed to the different physiological responses following instillation of solutions into the eye.     

DNA probe technology: implications for service planning in Britain

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.     

Rigid contact lens decentration: a risk factor for corneal warpage

Clinically significant contact lens induced corneal warpage is seen in a small proportion of soft and rigid contact lens wearers. Previous studies using the keratometer have found no correlation between the fit of the lens and the induced topographic changes. In this study, using computer-assisted topographic analysis, seven eyes (four patients) with rigid contact lens-induced corneal warpage were noted to have topographic abnormalities that correlated with the decentered resting position of the contact lens on the cornea. The warpage topography for each of these corneas was characterized by a relative flattening of the cornea underlying the resting position of the contact lens. Lenses that rode high, for example, produced flattening superiorly and resulted in a relatively steeper contour inferiorly that simulated the topography of early keratoconus patients who had not worn contact lenses. After discontinuing contact lenses the corneal topography returned to a normal pattern in five eyes. Two eyes retained asymmetry that is not characteristic of normal corneas. Up to 6 months was required for the corneas to return to a stable topography after contact lens wear was discontinued.     

The relationship between neuropsychological function and brain damage detected by neuroimaging after closed head injury

Studies relating neuropsychology and structural neuroimaging after closed head injury are reviewed. Particular attention is given to the question of the relative contribution of focal and diffuse damage to neuropsychological impairment. The evidence currently available emphasizes the importance of diffuse damage in closed head injury. Diffuse damage is not equally distributed in the brain, and the review suggests three axes that are relevant for neuropsychological function: (1) damage may be unilateral or bilateral, (2) damage is characteristically greater in anterior regions than posterior regions, and (3) damage shows a centripetal gradient. A large gap remains between the emergent generalizations concerning head injury and reliable neuropsychological interpretation of scans from individual patients.     

Endothelial function and aqueous humor flow rate in patients with Fuchs' dystrophy

Using a two-dimensional scanning fluorophotometer, we studied 50 subjects with symmetric ocular involvement of Fuchs' dystrophy without epithelial edema. Twenty-six subjects with confluent or nearly confluent cornea gutata with increased corneal thickness and 24 subjects with mild to moderate cornea guttata with normal corneal thickness were compared to normal control subjects. There were no statistically significant differences in endothelial permeability between the three groups. Corneal thickness was significantly increased in the subjects with confluent to nearly confluent guttae, however. These results suggest that endothelial pump function may be affected in subjects with advanced cornea guttata with stromal edema.     

Are Continuity Clinic Patients Less Satisfied When the Resident Is Postcall?

Due to recent public debate and newly imposed resident work hour restrictions, we decided to investigate the relationship of resident call status to their ambulatory patients' satisfaction. Resident continuity clinic patients were asked to rate their level of satisfaction on a 10-point Likert-type scale. Using multiple regression approaches, these data were then assessed as a function of resident call status. We found that in 646 patient encounters, patient satisfaction scores were significantly less when the resident was postcall, 8.99 ± 1.8, than when not postcall, 9.31 ± 1.3. We herein discuss etiologies and implications of these findings for both patient care and medical education.     

Effect of indomethacin on arachidonic acid metabolism in human leukocytes stimulated ex vivo.

We had previously shown that inhibition of cyclooxygenase in vitro by indomethacin can cause increased formation of products of the 5-lipoxygenase pathway of arachidonic acid metabolism in leukocytes. To determine if this effect also occurred in vivo, we studied leukocyte arachidonic acid metabolism in 12 volunteers before and after ingestion of 150 mg indomethacin daily for 3 days. Blood was collected before treatment and 2 hours, 2 days, and 5 days after the final dose of indomethacin. Serum thromboxane B2, a measure of platelet cyclooxygenase activity, was profoundly suppressed 2 hours after the final dose of indomethacin but had recovered to control values at 2 days. Mixed leukocyte suspensions and purified neutrophil suspensions were prepared and stimulated with calcium ionophore A23187 and the resultant 5-lipoxygenase metabolites were quantified by HPLC. Two hours after the final dose of indomethacin, the stimulated levels of 5-hydroxyeicosatetraenoic acid, leukotriene B4, and leukotriene C4 were significantly increased to 247% +/- 68%, 135% +/- 14%, and 149% +/- 23% of pretreatment values, respectively. Two days after the final dose of indomethacin, 5-hydroxyeicosatetraenoic acid levels were still significantly elevated. By 5 days all parameters had returned to baseline. Similar effects were not observed in purified neutrophil suspensions, probably because of the loss of indomethacin from the cells during the multiple washing procedures used in their preparation. This is in accord with the reversible nature of the inhibitory effect of indomethacin on cyclooxygenase. We conclude that indomethacin at a commonly used dose increases the ability of circulating leukocytes to produce 5-lipoxygenase products.     

Glutamergic Action on Alpha-Melanocyte-Stimulating Hormone Release from the Rat Hypothalamus

Release of α-melanocyte-stimulating hormone (α-MSH) synthesized in the hypothalamus is regulated by monoaminergic neuronal systems. An endogenous dopaminergic system inhibits α-MSH release (1, 2) whilst serotoninergic systems exert a biphasic effect on peptide release (3). The toxic effects of neonatal peripheral administration of monosodium glutamate on hypothalamic neurons containing proopiomelanocortin- (POMC-) derived peptides (4, 5) suggest additionally the presence of glutamate receptors on or indirectly influencing the POMC neuron. By comparison of the effect of the excitatory amino-acid agonists N-methyl-D-aspartate (NMDA), quisqualate and kainate on the release of α-MSH from superfused slices of rat hypothalamus, we have demonstrated a stimulatory glutamergic action on α-MSH release mediated through NMDA-type receptors.