Dark spots in late-phase indocyanine green angiographic studies in a patient with presumed ocular histoplasmosis syndrome

Purpose: We analyzed indocyanine green (ICG) angiograms in a patient with presumed ocular histoplasmosis syndrome (POHS) complaining about “seeing spots” and decreased visual acuity in order to identify the pathologic process. · Patients and methods: A 30-year-old caucasian man with clinical signs of POHS who had previously undergone laser photocoagulation for secondary choroidal neovascularization developed visual disturbances primarily in his temporal visual field. We performed fundus photography, fluorescein angiography and ICG angiography before, during and after the episode of visual disturbance. ICG angiographic findings were correlated to fundus photographs and fluorescein angiograms. · Results: Fundus examination, fluorescein angiograms and early-phase ICG angiograms were unremarkable at all time points. However, during the phase of visual disturbance, late-phase ICG angiographic study revealed hypofluorescent lesions in the area representing the visual disturbances. At 1 week follow-up, these hypofluorescent lesions were reduced in size and number; at 6 months follow-up they had completely resolved. · Conclusions: Late-phase ICG angiographic study can provide additional information in inflammatory retinal disease by virtue of identifying areas of choroidal alterations while standard diagnostic examination remain unremarkable. Received: 12 August 1998 Revised version received: 29 September 1998 Accepted: 29 September 1998     

Corneal astigmatism as a special complication after lid-loading in patients with lagophthalmos Hornhautastigmatismus als besondere Komplikation*

Lid-loading with precious metals, described by Illig in 1958, has become increasingly important. Because of its good functional and cosmetic results this method is superior to tarsorrhaphy. Furthermore, lid-loading can be combined with additional surgical techniques to achieve more dynamic lid-closure. In a prospective study we examined the results after lid-loading and discuss postoperative changes of the cornea.     

Optical penalization can improve vision after occlusion treatment

BACKGROUND: Optical penalization (OP) has previously been shown to successfully maintain vision in amblyopic eyes of older children when patching compliance is poor and when vision decreases once patching is discontinued. This study shows that the final vision in optically penalized eyes is often better than the vision obtained after patching alone. SUBJECTS AND METHODS: During the 5-year period from January 1992 to February 1997, 28 children aged between 3.7 and 8.2 years (average age, 6.5+/-1.1 years) were optically penalized for an average of 1.5+/-0.75 years. The maximum length of penalization was 3.3 years, whereas the minimum time was 6 months. There were 21 children with strabismic amblyopia and 7 children with anisometropic amblyopia. All 28 children had worn a patch to achieve their best visual levels and then had shown a loss of best vision when occlusion was stopped. Patching was usually resumed and continued until the previous best vision was obtained; at this point OP was started to "maintain" vision. Eighteen of the 28 children have discontinued penalization and have been followed up an average of 1(1/2) years. RESULTS: Twenty-six (93%) of the 28 patients showed an increase in best vision from that found at the conclusion of patching, and 2 patients maintained their vision at the initial level. The average visual acuity at the start of penalization was 20/50 (0.42+/-0.11 logarithm of the minimum angle of resolution [log MAR]). Final average visual acuity was 20/27 (0.15+/-0.12 log MAR). The average increase in vision was nearly 3 lines or 0.27+/-0.12 log MAR. CONCLUSION: OP alone (without the use of pharmacologic agents such as atropine) not only maintains vision after patching therapy, but also appears to improve the final visual outcome.     

The antifungal antibiotic clotrimazole potently inhibits L-type calcium current in guinea-pig ventricular myocytes.

The antimycotic agent clotrimazole (CLT) is a promising potential therapeutic agent for a variety of diseases including cancer. Although it is known that CLT alters calcium homeostasis in many cell types, its cardiac effects are virtually unknown. We investigated the effects of CLT on L-type calcium current (ICa,L) and action potentials in guinea-pig ventricular myocytes. CLT (5, 25 and 50 microM) inhibited basal ICa,L by 16, 59 and 93%, respectively. The inhibitory effect of CLT was rapid and the peak effect was attained within 3 min. At a concentration of 25 microM, the inhibitory effect of CLT was partially reversible whereas the response to 50 microM CLT persisted following drug withdrawal. CLT abbreviated action potential duration at 50 and 90% of repolarization and suppressed the plateau significantly. These results indicate that CLT may have important cardiac effects at concentrations used to induce the antiproliferative action of the drug.     

New classification and criteria for diagnosis of diabetes mellitus. The Australasian Working Party on Diagnostic Criteria for Diabetes Mellitus.

Diagnosis of diabetes is not in doubt when there are classical symptoms of thirst and polyuria and a random venous plasma glucose level > or =11.1 mmol/L. The Australasian Working Party on Diagnostic Criteria for Diabetes Mellitus recommends: Immediate adoption of the new criterion for diagnosis of diabetes as proposed by the American Diabetes Association (ADA) and the World Health Organization (WHO) - fasting venous plasma glucose level > or =7.0 mmol/L; Immediate adoption of the new classification for diabetes mellitus proposed by the ADA and WHO, which comprises four aetiological types - type 1, type 2, other specific types and gestational diabetes - with impaired glucose tolerance and impaired fasting glycaemia as stages in the natural history of disordered carbohydrate metabolism; Awareness that some cases of diabetes will be missed unless an oral glucose tolerance test (OGTT) is performed. If there is any suspicion or other risk factor suggesting glucose intolerance, the OGTT should continue to be used pending the final WHO recommendation.     

Ex-chiral pool synthesis and pharmacological aspects of 3-pyrrolidinylisoxazoles

Employing the dopamine autoreceptor agonist (-)-3-PPP (3) as well as the cholinergic receptor ligands 4 and 5 as lead compounds the 3-pyrrolidinylisoxazoles 2a,b as well as its optical antipodes ent 2a,b were synthesized from (R)-aspartic acid (6) and (S)-aspartic acid (ent-6), respectively. Pharmacological properties of the target compounds were evaluated employing dopamine D2 receptor binding studies and functional experiments on muscarinic M2 receptors.     

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects

Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity. Received: 8 March 1999 / Final version: 25 May 1999     

Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine

Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use. Received: 11 January 1999 / Final version: 25 March 1999     

Identification of urinary metabolites of isoprene in rats and comparison with mouse urinary metabolites.

Isoprene, a major commodity chemical used in production of polyisoprene elastomers, has been shown to be carcinogenic in rodents. Similar to findings for the structurally related compound butadiene, mice are more susceptible than rats to isoprene-induced toxicity and carcinogenicity. Although differences in uptake, and disposition of isoprene in rats and mice have been described, its in vivo biotransformation products have not been characterized in either species. The purpose of these studies was to identify the urinary metabolites of isoprene in Fischer 344 rats and compare these metabolites with those formed in male B6C3F1 mice. After i.p. administration of 64 mg [14C]isoprene/kg to rats and mice, isoprene was excreted unchanged in breath ( approximately 50%) or as urinary metabolites ( approximately 32%). In rats isoprene was primarily excreted in urine as 2-hydroxy-2-methyl-3-butenoic acid (53%), 2-methyl-3-buten-1,2-diol (23%), and the C-1 glucuronide conjugate of 2-methyl-3-buten-1,2-diol (13%). These metabolites are consistent with preferential oxidation of isoprene's methyl-substituted vinyl group. No oxidation of the unsubstituted vinyl group was observed. In addition to the isoprene metabolites found in rat urine, mouse urine contained numerous other isoprene metabolites with a larger percentage (25%) of total urinary radioactivity associated with an unidentified, polar fraction than in the rat (7%). Unlike butadiene, there was no evidence that glutathione conjugation played a significant role in the metabolism of isoprene in rats. Because of the unidentified metabolites in mouse urine, involvement of glutathione in the metabolism of isoprene in mice cannot be delineated.