Blur adaptation: clinical and refractive considerations

The human visual system is amenable to a number of adaptive processes; one such process, or collection of processes, is the adaptation to blur. Blur adaptation can be observed as an improvement in vision under degraded conditions, and these changes occur relatively rapidly following exposure to blur. The potential important future directions of this research area and the clinical implications of blur adaptation are discussed.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Pharmacological specificity of the caffeine discriminative stimulus in humans: effects of theophylline, methylphenidate and buspirone

The present study examined further the pharmacological specificity of the methylxanthine CNS stimulant caffeine as a discriminative stimulus in humans. Nine normal healthy volunteers (ages 19-39) were trained to discriminate between caffeine (320mg/70kg, p.o.) and placebo, using monetary reinforcement of correct letter code identification. After four training sessions, subjects were tested with the training conditions until they were >80% correct on four consecutive sessions. Then dose-effect curves were determined for caffeine (56-320mg/70kg), theophylline (56-320mg/70kg), methylphenidate (10-56mg/70kg), and buspirone (1-32mg/70kg). Seven of nine subjects met the discrimination criterion within four to nine sessions. During dose-effect curve determinations, caffeine and methylphenidate each produced dose-related increases in caffeine-appropriate responding. Theophylline produced caffeine-appropriate responding that was not dose related in a consistent manner across subjects, occasioning an average of 50% caffeine-appropriate responding at most doses tested. Buspirone produced predominantly placebo-appropriate responding. Caffeine-appropriate responding tended to be directly related to ARCI LSD scores, self-reported "bad" effects, "high", and stimulant-bad effects and inversely related to ARCI PCAG scores and sedative ratings. These results agree with non-human data and suggest that the caffeine discriminative stimulus has pharmacological specificity, in that caffeine-appropriate responding generalizes to other stimulants such as theophylline or methylphenidate, but not to non-stimulant compounds such as buspirone.     

Effects of diazepam and hydromorphone in triazolam-trained humans under a novel-response drug discrimination procedure

Seven healthy normal male and female volunteers (21–31 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg, PO; e.g., drug A) and placebo (e.g., drug B) under a three-choice, instructed novel response drug discrimination procedure. Once the criterion for discrimination was met (i.e., >85% correct responding on four consecutive sessions), dose-effect curves were determined for triazolam (0.1–0.56 mg/70 kg), the benzodiazepine diazepam (10–32 mg/70 kg) and the opioid agonist hydromorphone (1–6 mg/70 kg). Subjects met the criterion for discrimination within four to six sessions. Triazolam and diazepam produced dose-related increases in triazolam-appropriate responding and no novel-appropriate responding at any dose tested. In contrast, hydromorphone generally increased novel-appropriate responding in a dose-related manner, with placebo-appropriate responding and some triazolam-appropriate responding at intermediate doses occurring also. Triazolam and diazepam produced qualitatively similar increases on several measures of sedative drug effects; hydromorphone increased ratings of like novel and sedative-like effects in subjects who discriminated hydromorphone as novel relative to those who did not. These results indicate that the novel response drug discrimination procedure enhances the specificity of the triazolam-placebo discrimination.This work was supported by USPH grants DA-06205, T32-DA-07242 and Research Scientist Development Award DA-00109 (J.R.H.) from the National Institute on Drug Abuse.     

The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.