Corneal desiccation staining with hydrogel lenses: Tear film and contact lens factors

This investigation monitored the response of established contact lens wearers using contact lenses made from Filcon 4a 77% water-content material in three different thicknesses (0.08, 0.10 and 0.12 mm) over a 6-hour period of wear under adverse environmental conditions. The results obtained showed the following. (1) In accordance with previous studies carried out with lenses of similar water content, the present lenses produced corneal desiccation staining under the challenging conditions of use. However, the staining produced was similar for all three lens thicknesses tested. (2) Corneal desiccation staining was present despite the good and stable fitting characteristics observed during the study, confirming that mechanical trauma is not a necessary cause for soft-lens-induced desiccation staining. (3) Corneal desiccation staining was associated with a rapidly destabilizing pre-lens tear film (PLTF) and a thinning lipid layer. The initial break-up of the PLTF and corneal staining were recorded with a higher incidence in the vertical quadrants than in the horizontal quadrants. The PLTF is thinnest and most unstable at the tear prism margin border, hence least efficacious at preventing evaporation. Corneal desiccation staining may be due, at least partly, to excessive evaporation at the contact lens front surface.     

Isometric muscle strength is an indicator of self-reported physical functional disability in patients with rheumatoid arthritis

The objective of our study was to examine (1) whether isometric muscle strength contributes to the explanation of the physical functional disability of a rheumatoid arthritis (RA) patient population after accounting for other disease parameters and demographic variables and (2) whether change in isometric muscle strength is an indicator of change in physical functional disability. Sixty-five consecutive patients fulfilling the American Rheumatism Association 1987 revised criteria for RA were included in the study. Isometric muscle strength was measured with a validated Muscle Strength Index (MSI) calculated as the mean score of standardized isometric extension and flexion strength of the knee and elbow joints. Physical functional disability was measured with the physical dimension of the Health Assessment Questionnaire (HAQ). For 56 patients, we could obtain 1 yr follow-up data. Cross-sectionally, there was a significant correlation (r = - 0.51, P < 0.01) between the MSI and the HAQ. Muscle strength remained a significant determinant of the HAQ in multivariate analysis accounting for disease and demographic variables. Longitudinally, change in MSI explained additional variance of change in HAQ after accounting for change in pain, the most important correlate of change in HAQ.      

Different clinical types of degenerative aphasia

The authors report 3 cases of slowly progressive aphasia with different language disturbances: anomia, pure word deafness and Broca's aphasia. All patients were independent in daily life activities. Insight, judgement and overall behaviour were intact. There was no major disturbance of other cognitive functions, but psychometric tests showed mild deficits suggesting widespread involvement. CT scans and magnetic resonance imaging showed focal dilatation of the left sylvian fissure. A positron emission tomographic study showed left perisylvian hypometabolism. A review of the literature yielded an increasing number of cases of this degenerative syndrome affecting dominant hemisphere language areas. Our cases confirm the clinical heterogeneity of degenerative aphasia. Postmortem neuropathological examinations are rare and many causes are found: Pick's disease, Alzheimer's disease or aspecific gliosis.     

Chequerboard titrations: the influence of the composition of serial dilutions of antibiotics on the fractional inhibitory concentration index and fractional bactericidal concentration index

Chequerboard titrations carried out with modified serial dilutions of antibiotics such that consecutive concentrations in these series were four times smaller than those in two-fold serial dilutions enable MICs and MBCs to be determined with greater accuracy. Interaction indices calculated by this method can differ markedly from those calculated on the basis of two-fold serial dilutions. The differences calculated in this study ranged from -0.30 to +1.06.     

Norfloxacin: clinical pharmacology and clinical use

Norfloxacin, a nalidixic acid analog, is the first of the fluorinated quinolinecarboxylic acids to be marketed in the United States. It demonstrates potent antibacterial activity against aerobic, gram-negative bacteria including the Enterobacteriaceae, gentamicin-resistant Pseudomonas aeruginosa, and penicillin-resistant Neisseria gonorrhoeae. Norfloxacin exhibits good activity against methicillin-resistant and -sensitive Staphylococcus aureus, but less activity against most other aerobic, gram-positive organisms. Anaerobic bacteria are resistant to the drug. Resistance to norfloxacin is not plasmid mediated, but is secondary to bacterial mutation, and occurs less frequently than nalidixic acid resistance. Its pharmacokinetic properties after a 400-mg oral dose consist of a peak serum concentration of 1.3-1.58 micrograms/ml, an elimination half-life of 3-7 hours, and good penetration into kidney and prostatic tissues. Renal excretion is the major route of elimination. Norfloxacin is highly effective in the treatment of uncomplicated and complicated urinary tract infections, and gonococcal urethritis. Adverse effects are generally well tolerated and usually do not require discontinuation of therapy.     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995     

Effects on Behaviour and EEG of Single Chain Phospholipases A2 from Snake and Bee Venoms Injected into Rat Brain: Search for a Functional Antagonism

Abstract: Three phospholipase A₂ (PLA₂s), OS₁ and OS₁ purified from the taipan snake venom Oxyuranus scutellatus scutellatus and bee venom PLA₂ were injected to rats by the intracerebroventricular route. OS₁ showed no sign of neurotoxicity at doses at which OS₂ and bee venom PLA₂ produced multiform dose-dependent behavioural effects including motor disturbances (stereotyped movements), compulsive scratching, convulsions and breathing difficulties. EEG recordings showed at the very time when the animal was motionless the induction of several episodes of a low frequency hippocampal theta rhythm, index of long-term changes in synaptic neuroplasticity. Spike-wave discharges were also produced but the occurrence was not systematic. These seizures were often accompanied with behavioural convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic transmission could not abolish the neurotoxic effects of PLA₂s except for diazepam (10 mg/kg intraperitoneally) that prevented only OS₂-induced disturbances. Blockers of L-type Ca²⁺ channels and K⁺ channel openers were also without effect. The toxicity of OS₂ and bee venom PLA₂ is probably due to their initial specific binding to their neuronal receptor sites.     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.