Cellular basis for progesterone neuroprotection in the injured spinal cord

Progesterone (PROG) exerts beneficial and neuroprotective effects in the injured central and peripheral nervous system. In the present work, we examine PROG effects on three measures of neuronal function under negative regulation (choline acetyltransferase [ChAT] and Na,K-ATPase) or stimulated (growth-associated protein [GAP-43]) after acute spinal cord transection injury in rats. As expected, spinal cord injury reduced ChAT immunostaining intensity of ventral horn neurons. A 3-day course of intensive PROG treatment of transected rats restored ChAT immunoreactivity, as assessed by frequency histograms that recorded shifts from predominantly light neuronal staining to medium, dark or intense staining typical of control rats. Transection also reduced the expression of the mRNA for the alpha3 catalytic and beta1 regulatory subunits of neuronal Na,K-ATPase, whereas PROG treatment restored both subunit mRNA to normal levels. Additionally, the upregulation observed for GAP-43 mRNA in ventral horn neurons in spinal cord-transected rats, was further enhanced by PROG administration. In no case did PROG modify ChAT immunoreactivity, Na,K-ATPase subunit mRNA or GAP-43 mRNA in control, sham-operated rats. Further, the PROG-mediated effects on these three markers were observed in large, presumably Lamina IX motoneurons, as well as in smaller neurons measuring approximately <500 micro2. Overall, the stimulatory effects of PROG on ChAT appears to replenish acetylcholine, with its stimulatory effects on Na,K-ATPase seems capable of restoring membrane potential, ion transport and nutrient uptake. PROG effects on GAP-43 also appear to accelerate reparative responses to injury. As the cellular basis for PROG neuroprotection becomes better understood it may prove of therapeutic benefit to spinal cord injury patients.     

Optic disk drusen

Optic disk drusen occur in 3.4 to 24 per 1,000 population and are bilateral in approximately 75%. Disturbance in the axonal metabolism in the presence of a small scleral canal—regardless of eyelength—is considered responsible for the development. The drusen increase in size, becoming more visible with age due to continuing calcium apposition, and they are associated with visual field defects in a considerable number of patients. Patients do not usually notice these defects, despite their progressive nature over the years, and this indicates an insidious course. A correct diagnosis of optic disk drusen is mandatory, although effective treatment is not yet available. It is most important to differentiate optic disk drusen from papilledema in order to avoid unnecessary neurological examinations, but also to avoid overlooking genuine neurologic disorders. Because optic disk drusen can cause severe visual field defects, patients require individual consultation regarding work issues and whether or not to drive. Optic disk drusen can be accompanied by vascular complications as well. In some cases these vascular changes—for example, choroidal neovascularization—are treatable. Patients with optic disk drusen should undergo regular visual field, IOP, and nerve fiber layer examinations. In patients with deteriorating visual field and borderline IOP, we recommend antiglaucomatous therapy.     

The learning effect in visual field testing of healthy subjects using frequency doubling technology

PURPOSE: To evaluate the presence, duration and magnitude of a learning effect in serial visual field (VF) testing, using the commercially available frequency doubling technology (FDT) instrument. PATIENTS AND METHODS: 21 healthy adults with no prior VF experience underwent 6 serial VF tests, using the full-threshold C-20 program of the Zeiss-Humphrey FDT analyzer, on one randomly chosen eye. Tests were spaced at least two days apart. RESULTS: The average mean sensitivity was 32.37 +/- 2.6 dB; the average mean deviation (MD) was 1.22 +/- 1.8 dB. The MD at the first examination (0.28 +/- 2.1 dB) was significantly poorer than at any of the other testing sessions (p<0.003). Similarly, the mean sensitivity at the first examination (31.16 +/- 3.0 dB) was significantly lower than any other testing session (p<0.004). The proportion of improvement from the first to the second session was 63% and 65% of the total improvement, for mean sensitivity and MD, respectively. Mean test duration showed a modest reduction, from 4.40 +/- 0.3 minutes in the first session to 4.17 +/- 0.4 minutes in the last session (p = 0.023). A sub-analysis comparison of the different VF segments showed a more prominent learning effect in the peripheral and nasal visual segments (p<0.0001). CONCLUSION: Baseline measurements should best rely on the second testing session, since MD and mean sensitivity are somewhat poorer when subjects with no prior VF experience are first tested on the FDT instrument. This may be especially true for the purpose of following patients over time.     

Emergency treatment of chemical and thermal eye burns

Chemical and thermal eye burns account for a small but significant fraction of ocular trauma. The speed at which initial irrigation of the eye begins, has the greatest influence on the prognosis and outcome of eye burns. Water is commonly recommended as an irrigation fluid. However, water is hypotonic to the corneal stroma. The osmolarity gradient causes an increased water influx into the cornea and the invasion of the corrosive substance into deeper corneal structures. We therefore recommend higher osmolarities for the initial rinsing to mobilize water and the dissolved corrosives out of the burnt tissue. Universal systems such as amphoteric solutions, which have an unspecific binding with bases and acids, provide a convenient solution for emergency neutralisation. Both conservative anti-inflammatory therapy and early surgical intervention are important to reduce the inflammatory response of the burnt tissue. In most severe eye burns, tenonplasty re-establishes the conjunctival surface and limbal vascularity and prevents anterior segment necrosis.     

Secondary cataract treatment with laser YAG-ND

The purpose of the study is to present the favorable results of YAG: Nd laser capsulotomy for the treatment of secondary opacification of the posterior capsule, in our department. A 3 years retrospective study was performed. For 1440 cataract operations, most of them extracapsular extractions with PMMA IOL placed in the posterior chamber (ciliary sulcus or capsular bag), 285 laser capsulotomies were done. The results are presented statistically, including sex and age distribution, type of cataract surgery and implant, treatment protocol (number of sessions, number of impulses per session, energy per impulse) and complications. The frequency of secondary capsular opacification in our study is 19.78%. It is most important in the age group 60-70 years, where the surgery for cataract is performed more often. Capsulotomy was done after extracapsular extraction with IOL placed in the posterior chamber, but especially after extracapsular extraction without implant placement or with complications that have permitted only the use of an anterior chamber implant. Capsulotomy is performed in only one session in 88% of the cases. The energy per impulse is usually 3-5 mJ and the mean number of impulses per session is 10-30. There are few complications: transient elevation of intraocular pressure in 14.73%, discrete laser marks on the implant in 8.77% and moderate iritis in 1% of the cases. YAG: Nd laser capsulotomy appears to be a safe and efficient method of treating secondary cataract; it improved visual acuity in all cases, if different ocular pathology had not influenced it.     

Idiopathic eosinophilic orbital pseudotumor of the lacrimal gland in a child

BACKGROUND: Idiopathic orbital pseudotumor is a rare disease. 10 % of the cases occur in children. In most of these juvenile cases, the swelling is bilateral, and histologically, eosinophilic granulocytes are found. In contrast to adults, children very rarely develop an associated systemic disorder. The disease is generally treated with steroids. Little is known about the natural course of idiopathic orbital pseudotumors in childhood. PATIENT: A 2S-year old girl presented with a unilateral swelling of the right upper lid. Four weeks later, a comparable swelling of the left side was revealed. We took biopsies of the lacrimal gland on both sides. Histology displayed an eosinophilic pseudotumor of the lacrimal gland. Steroid treatment was started, but after 4 weeks the parents refused to continue the treatment. During the following year, the bilateral swelling remained unchanged. Surprisingly, the bilateral swelling disappeared 3 years later and no systemic disorder had occured. CONCLUSIONS: Our case shows that spontaneous resolution of a juvenile eosinophilic orbital pseudotumor is possible. Treatment with steroids does not appear to be compulsory in all cases.     

Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin

PURPOSE: The degeneration of retinal pigment epithelial (RPE) cells is considered to be a crucial event in the pathophysiology of age-related macular degeneration (AMD). Cumulative oxidative damage has been implicated in the development of the changes seen in AMD. The present study was undertaken to evaluate the expression of the small heat shock protein alphaB-crystallin in the RPE in response to oxidative stress and to explore whether alphaB-crystallin expression confers an antiapoptotic cytoprotective effect on RPE cells. METHODS: Native human RPE cells from the macula and retinal periphery were analyzed by RT-PCR and Western blot analysis for expression of alphaB-crystallin. Monolayer cultures of human RPE cells were stressed by heat shock (42 degrees C for 20 minutes) or oxidant-mediated injury (50-300 micro M H(2)O(2) for 1 hour). Induction of alphaB-crystallin and the corresponding mRNA was assessed by Western and Northern blot analyses. To study the cytoprotective effect of alphaB-crystallin, human RPE cells were transfected with either a neomycin-selectable expression vector containing alphaB-crystallin cDNA or a control vector without alphaB-crystallin cDNA. Caspase-3 activity was determined by observing the cleavage of a colorimetric peptide substrate. Cell viability was quantified by combined propidium iodide and Hoechst 33342 staining. RESULTS: alphaB-crystallin is constitutively expressed in RPE under in vivo and in vitro conditions. Western blot analysis of freshly isolated RPE showed greater baseline expression levels in RPE derived from the macular area than in that from the more peripheral regions. Heat shock treatment and oxidative stress caused a significant increase in alphaB-crystallin mRNA and protein. Oxidant-mediated injury in RPE cells with baseline expression levels of alphaB-crystallin resulted in apoptotic cell death, as measured by caspase-3 activity, whereas RPE cells that had been stably transfected with alphaB-crystallin were more resistant to H(2)O(2)-induced cellular injury. CONCLUSIONS: alphaB-crystallin may function as a stress-inducible antiapoptotic protein in human RPE and is inducible by oxidative stress, a condition implicated in the pathogenesis of AMD. Overexpression of alphaB-crystallin may be an important mechanism for the RPE to prevent apoptotic cell death in response to cellular stress.     

Residence time of netilmicin in tears.

PURPOSE: To determine the concentration of netilmicin in tears after eye drop administration. METHODS: A clinical study was carried out on 32 healthy volunteers. Subjects were divided into four groups and underwent tear collection at 5, 10, 20, and 60-minutes after drug administration, respectively. Tear samples were collected through capillary suction from the inferior conjunctival "cul-de-sac" and analyzed by high-pressure liquid chromatography (HPLC). RESULTS: Netilmicin concentration in tears decreased after a first order kinetics, a best-fit curve was drawn and the minimum inhibitory concentration (MIC90) intersection for the most common ocular pathogens was calculated. CONCLUSIONS: The extrapolation of the curve shows that the concentration of netilmicin on the ocular surface can be effective against microorganisms more than 120 minutes after eye drop instillation.     

The relationship between two intermediate phenotypes for alcoholism: low voltage alpha EEG and low P300 ERP amplitude

OBJECTIVE: There is considerable evidence that the amplitude of the heritable P300 event-related potential (ERP) is reduced in alcoholics and their alcohol-naive children. Low voltage alpha (LVA), a heritable resting electroencephalogram (EEG) trait present in 7-14% of the population, has been shown to be associated with alcoholism and anxiety disorders. A few studies have demonstrated a modest correlation between pre-stimulus alpha power and P300 amplitude. We aimed to test this finding in community volunteers, hypothesizing that LVA would be associated with low P300 amplitude. METHOD: Digitized resting EEG was recorded at the central parietal site (Pz) from 85 male and 113 female community volunteers (120 unrelated). ERPs were elicited at Pz by auditory and visual oddball paradigms. All participants were interviewed with the Schedule for Affective Disorders, Lifetime Version (SADS-L) and assigned blind-rated psychiatric diagnoses according to the American Psychiatric Association DSM-III-R criteria. RESULTS: LVA participants (including alcoholics and nonalcoholics) had significantly lower auditory and visual P300 amplitudes. Absolute alpha power was modestly correlated with auditory and visual P300 amplitude and was associated with 9.4% and 4.6% of the variance, respectively. CONCLUSIONS: The association between LVA and low P300 amplitude, two distinct electrophysiological traits, suggests that, at least in individuals with the LVA trait, some aspects of resting, unstimulated brain activity and activated brain function in the form of attentional response may be fundamentally related.