[Giant cell arteritis (temporal arteritis, Horton's arteritis): clinical characteristics and management]. / Morbus Horton (Arteriitis temporalis, Riesenzellarteriitis): Klinik, Diagnostik, Histologie, Therapie.

Giant cell arteritis can cause diagnostic difficulties due to its heterogeneous symptomatology. Characteristic ophthalmic and systemic symptoms of Horton's disease are discussed. The clinical course is described on the basis of typical patients, which shows that generic symptoms do not have to coexist. The Horton's arteritis potentially represents a systemic vasculitis that requires early diagnosis and treatment in order to avoid dramatic ophthalmic consequences, in worst cases blindness. The erythrocyte sedimentation rate (ESR) represents the most important laboratory parameter. Although temporal artery biopsy remains the only confirmatory procedure for a definite diagnosis, imaging procedures such as sonography, magnetic resonance imaging, ultrasound biomicroscopy are useful in supporting the clinical diagnosis. Highly dosed corticosteroid therapy should always be indicated when suspicious clinical symptoms are present, even without any dramatic laboratory parameter changes. Initial high dosages are indicated up to 1 gram daily depending on the severity of the disease. Subsequently a slow ESR titrated reduction of the dose is necessary under control of inflammation values, symptomatology and side effects. Occasionally a lifelong immunsuppressive therapy is indispensable. The long-term treatment should take place in close cooperation with the general practitioner, rheumatologist, neurologist and if necessary further specialists.

In an emergency--call the clinical librarian!

This paper reviews the role of the clinical librarian in the emergency department.

Prediction of mortality in adult emergency department patients with sepsis.

OBJECTIVES: To determine the efficacy of the abbreviated Mortality in Emergency Department Sepsis (MEDS) score, the Modified Early Warning (MEW) score and near-patient-test (NPT) lactate levels in predicting 28-day mortality in adult emergency department (ED) patients with sepsis. METHODS: A retrospective cohort study of adult ED patients with sepsis admitted to hospital was conducted in a large urban teaching and a district general hospital. Data were collected during four time periods between 1 January 2006 and 31 January 2007. Inclusion criteria were age > or =16 years and an ED diagnosis of sepsis. Primary outcome for all patients was 28-day mortality. Patients were preassigned to risk groups according to their abbreviated MEDS score, MEW score and NPT lactate. RESULTS: 307 ED patients with sepsis were included in the study. Among these there were 72 deaths (23%). Mortality rates for the low-, moderate- and high-risk groups of the abbreviated MEDS score were 1/63 (1.6%), 48/205 (23.4%) and 23/39 (59.0%) patients. The MEDS score for low-risk patients was 98.6% (95% CI 92.5% to 99.9%) sensitive and 26.5% (95% CI 21.0% to 32.6%) specific and for high-risk patients it was 31.9% (95% CI 21.4% to 44.0%) sensitive and 93.2% (95% CI 89.2% to 96.1%) specific for death within 28 days. Mortality rates for the low- and high-risk MEW score were 20/159 (12.6%) and 52/148 (35.1%) patients. The MEW score for high-risk patients was 72.2% (95% CI 60.4% to 82.1%) sensitive and 59.2% (95% CI 52.6% to 65.5%) specific for mortality. An NPT lactate level of > or =4 mmol/l was 49.1% (95% CI 35.1% to 63.2%) sensitive and 74.3% (95% CI 64.8% to 82.3%) specific for 28-day mortality. CONCLUSION: These results demonstrate the efficacy of the abbreviated MEDS score, the MEW score and NPT venous lactate levels in predicting 28-day mortality in ED patients with sepsis. The abbreviated MEDS score was found to be the best performing risk assessment model which, with prospective validation, may aid early clinical decision-making in ED patients with sepsis and might affect the outcome from sepsis.

Use of helium-oxygen mixtures in the treatment of croup: a systematic review.

OBJECTIVE: To determine the effect of helium-oxygen inhalation on relieving symptoms and distress in children with croup as measured by the croup score, and to identify areas of uncertainty for future research. METHODS: Systematic review of prospective randomised and non-randomised controlled trials of children with the clinical diagnosis of croup, comparing the effect of helium-oxygen mixtures with placebo or any active treatment. Outcome measures were change in croup score, physiological parameters, hospital admission rates, need for intubation and adverse events. All records as identified by a systematic search strategy were assessed independently by two reviewers. RESULTS: Two trials were identified for inclusion assessing the effect of helium-oxygen inhalation in children with croup in an emergency department. In one trial the control group received humidified oxygen and in the other nebulised epinephrine. An improvement in the mean croup score over time was seen in the control and intervention groups of both trials, with no significant difference between the groups. Significant methodological and clinical heterogeneity in the design of the trials precluded a meaningful meta-analysis. CONCLUSION: At present there is no evidence to support the use of helium-oxygen therapy in children with croup. Methodologically well-designed and adequately powered randomised controlled trials are needed to determine whether helium-oxygen inhalation as part of the initial treatment in croup alters outcome.

[A comparison of rebound tonometry (ICare) with TonoPenXL and Goldmann applanation tonometry]. / Evaluierung der Reboundtonometrie (ICare) im Vergleich zum TonopenXL und dem Goldmann-Applanationstonometer.

BACKGROUND: Goldmann applanation tonometry and dynamic contour tonometry (PASCAL) are two well established slit lamp mounted tonometric methods. Intraocular pressure measurement in bedridden patients and children is often only possible using hand held tonometers (TonoPenXL, Perkins tonometer, Draeger tonometer). This study was performed to evaluate the hand held ICare tonometer, which is based on the rebound method. METHODS: A total of 102 eyes were examined by two highly experienced ophthalmologists for: 1) ophthalmological status, 2) central corneal power (Zeiss IOL-Master), 3) central corneal thickness (Tomey ultrasound pachymetry, five successive measurements, SD<5%), 4) intraocular pressure (IOP) measurement with the Goldmann applantation tonometer (GAT) 1x, 5) TonoPenXL (1x), 6) ICare with three successive measurement series of 6 single measurements. RESULTS: The mean IOP(GAT) was 13.2+/-3.0 mmHg compared with the mean IOP(TonoPenXL) (13.4+/-3.1 mmHg) and with the IOP(ICare) (mean value of first measurement series: 13.4+/-3.1 mmHg). The series of measurements with the ICare showed a tonography effect (decrease of IOP from 14.6 mmHg at the first measurement and 14.2 mmHg at the second to 14.0 at the third measurement). The ICare-measurements were highly reliable (Cronbach's alpha=0.974) and showed a good correlation between the measurement series (r=0.592-0.642; p<0.001). There was a great intra-individual variability of up to 17 mmHg between the GAT, TonoPenXL and ICare methods. CONCLUSIONS: The ICare tonometer is easy to handle and high reliability. The data are comparable with those from the Goldmann tonometer. A tonography effect of 0.6 mmHg in the successive measurement series was found.

Pineal epidermoid coinciding with pineocytoma.

Tumours of the pineal region are uncommon. We report on a 62-year-old male presenting with Parinaud's syndrome and aqueduct stenosis caused by a cystic tumour in the pineal region. During surgery, adjacent to the cystic tumour, a second smaller tumour was identified, which was clearly separate from the first tumour and from the pineal gland. Histological examination disclosed the cystic tumour as an epidermoid cyst, whereas the second tumour demonstrated histological and immunohistochemical features of a pineocytoma. The unique finding of two different types of tumours in the pineal region is evaluated with regard to the histogenesis of epidermoid cysts and pineocytomas.

[Quantitative and objective topometrical analysis of drusen of the optic nerve head with the Heidelberg retina tomograph (HRT)]. / Quantitative und objektive topo-metrische Analyse von Drusenpapillen mit dem Heidelberg-Retina-Tomographen (HRT).

BACKGROUND AND PURPOSE: Optic nerve head drusen (ONHD) are one of the most frequent causes for congenital swelling of the optic nerve head. Visual field and retinal nerve fiber layer defects are reported in cases of ONHD. The Heidelberg Retina Tomograph (HRT) allows a 3-dimensional topometric analysis of the optic nerve disc and measurement of the peripapillary mean retinal nerve fiber layer. PATIENTS AND METHODS: A total of 18 eyes from 9 patients with sonographically confirmed drusen were analyzed with the HRT. Data were compared to a control group of 18 eyes from 9 matched healthy individuals. Statistical analyses were performed by using ANOVA (univariate). All patients with ONHD underwent a computerised visual field test (30 degrees, Octopus 101). Due to a bad reliability factor of over 10 in the visual fields by 4 out of 18 eyes, only measurements from 14 eyes were included in the study. We correlated visual field and HRT parameters and calculated the Pearson's correlation coefficient (r). RESULTS: We found a significant difference in the measured parameter mean retinal nerve fiber layer (RNFL) thickness ( p<0.05) between the two groups. In the ONHD group a negative correlation coefficient was found between the peripapillary mean RNFL thickness and the loss variance (r=-0.50, p=0.03) as well as between the peripapillary RNFL cross-sectional area and the loss variance (r=-0.47, p=0.04). CONCLUSIONS: The HRT is able to detect a peripapillary RNFL thinning in cases with ONHD. The mean RNFL thickness correlated with the loss variance. The HRT should be used to perform a quantitative and objective topometric analysis in cases with ONHD.

Excitotoxicity can be mediated through an interaction within the optic nerve; activation of cell body NMDA receptors is not required.

Axonal trauma leads to a series of pathologic events that can culminate in neuronal death. Although the precise mechanisms of retinal ganglion cell death after optic nerve crush in the rat model have not been elucidated, glutamate antagonists can protect retinal ganglion cells after optic nerve axotomy. We therefore explored whether a glutamate congener was toxic if applied directly within the optic nerve, or if toxicity depended upon an interaction at the cell body level. NMDA reduced retinal ganglion cell survival when applied directly into the rat optic nerve. Glutamate can be toxic if administered within the optic nerve; a direct effect at the cell body is not necessary. Future work will help to additionally unravel the steps by which axotomy induces excitotoxic damage to ganglion cells, and perhaps indicate protective interventions.

Ganglioside patterns in human spinal cord.

OBJECTIVE: To examine the distribution of gangliosides in human cervical and lumbar spinal cord. SETTING: Magdeburg, Germany. METHODS: The ganglioside distribution of human cervical and lumbar spinal cord enlargements from 10 neurological normal patients was analyzed. Gangliosides were isolated from different areas corresponding to the columna anterior, columna lateralis and columna posterior. RESULTS: Ganglioside GfD1b/GD1b and GD3 were the most abundant gangliosides in all examined tissues. The total concentration of sialic acid bound gangliosides GM2 and GM3 was less than 5%. The GD3 fraction constantly consisted of a double band as assessed by TLC after lipid extraction. There were significant differences in the ganglioside distribution when comparing tissue from the columna anterior, columna lateralis and columna posterior of the lumbar enlargement of the spinal cord. CONCLUSION: Differences in the ganglioside composition in human spinal cord regions may reflect the different function of those molecules in the two regions investigated.

Ganglion cell loss after optic nerve crush mediated through AMPA-kainate and NMDA receptors.

PURPOSE: Glutamate antagonists can block ganglion cell death due to optic nerve crush. Although most investigators have focused on blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, we have chosen to evaluate the efficacy of blockade of the AMPA-kainate (KA) receptor in this experimental paradigm. METHODS: The optic nerves of rats were crushed, and ganglion cell survival was assessed. Groups of animals were treated with an NMDA antagonist, an AMPA-KA antagonist, or both. RESULTS: The AMPA-KA antagonist DNQX was more effective, although not additive in preserving retinal ganglion cells after optic nerve crush than the NMDA antagonist MK801. CONCLUSIONS: Activation of the AMPA-KA subtype of glutamate receptor may play a role in glutamate-mediated cell death after optic nerve crush.

Depression of retinal glutamate transporter function leads to elevated intravitreal glutamate levels and ganglion cell death.

PURPOSE: Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters (molecules that ordinarily regulate extracellular glutamate; E:xcitatory A:mino A:cid T:ransporter; EAAT). Elevated glutamate levels can also lead to alterations in glutamate receptor expression. It was hypothesized that selective blockade of glutamate transporters would be toxic to retinal ganglion cells. METHODS: Glutamate transporters were blocked either pharmacologically or with subtype-specific antisense oligonucleotides against EAAT1. Glutamate levels, transporter levels and ganglion cell survival were assayed. RESULTS: Pharmacological inhibition of glutamate transporters with either an EAAT2 specific inhibitor or a nonspecific inhibitor of all the subtypes of transporters was toxic to ganglion cells. Treatment with oligonucleotides against the glutamate transporter EAAT1 decreased the levels of expression of the transporter, increased vitreal glutamate, and was toxic to ganglion cells. CONCLUSIONS: These results demonstrate that normal function of EAAT1 and EAAT2 is necessary for retinal ganglion cell survival and plays an important role in retinal excitotoxicity. Manipulation of retinal glutamate transporter expression may become a useful tool in understanding retinal neuronal loss.

Concurrent downregulation of a glutamate transporter and receptor in glaucoma.

PURPOSE: Elevated levels of extracellular glutamate have been implicated in the pathophysiology of neuronal loss in both central nervous system and ophthalmic disorders, including glaucoma. This increase in glutamate may result from a failure of glutamate transporters, which are molecules that ordinarily regulate extracellular glutamate. Elevated glutamate levels can also lead to a perturbation in glutamate receptors. The hypothesis for the current study was that glutamate transporters and/or receptors are altered in human glaucoma. METHODS: Immunohistochemical analyses of human eyes with glaucoma and control eyes were performed to evaluate glutamate receptors and transporters. These molecules were also assayed in rat eyes injected with glial-derived neurotrophic factor (GDNF). RESULTS: Glaucomatous eyes had decreased levels of both the glutamate transporter, excitatory amino acid transporter (EAAT)-1, and the glutamate receptor subunit N-methyl-D-aspartate (NMDA)-R1. Eyes treated with GDNF had elevated levels of both EAAT1 and NMDAR1. CONCLUSIONS: The loss of EAAT1 in glaucoma may account for the elevated level of glutamate found in glaucomatous vitreous and lead to a compensatory downregulation of NMDAR1. Inasmuch as GDNF can increase levels of both EAAT1 and NMDAR1, it may be a useful therapeutic approach to restore homeostatic levels of these in glaucoma.

Thy-1 is critical for normal retinal development.

In the mammalian retina, Thy-1, the most abundant mammalian neuronal surface glycoprotein, is found predominantly if not exclusively on retinal ganglion cells. We hypothesized that Thy-1 plays a significant role in retinal development. Neurite outgrowth of retinal ganglion cells from Thy-1(-) mice over multiple substrates was compared to that seen with wild-type controls. Adult mouse retinas were histologically compared between Thy-1(-) and three strains of Thy-1 positive mice. Thy-1(-) retinal ganglion cells had significantly less neurite outgrowth than controls. The inner nuclear, inner plexiform, ganglion cell and outer segment/pigment epithelium layers were thinner in Thy-1(-) retinae than in controls. Thy-1 appears to be critical for normal retinal development.

Infection with adeno-associated virus may protect against excitotoxicity.

Gene therapy has developed as a promising approach for therapy in a broad variety of conditions. Viral vectors have been developed that may replace a defective gene, prevent expression of a mutant gene, or deliver a protective gene and thereby delay cellular loss. Using adeno-associated virus containing green fluorescent protein (AAV-GFP) we were able to specifically transduce cells located in the inner retina and induce over-expression of GFP in adult rat retinae. The delivery and expression of GFP had no influence themselves on retinal ganglion cell survival. Administration of the reporter vector AAV-GFP provided retinal ganglion cells with slight but significant protection from intravitreal NMDA. This was a locally mediated phenomenon; greater protection was seen in regions with more transduced cells. Any evaluation of the efficacy of a putative viral vector should consider the possible protective or toxic effect of the native virus.

Susceptibility of retinal ganglion cells to excitotoxicity depends on soma size and retinal eccentricity.

PURPOSE: This study was undertaken to determine if retinal ganglion cell sensitivity to intraocular N-methyl-D-aspartate or kainate injections varied as a function of retinal location (eccentricity) or cell soma size. METHODS: Rat retinal ganglion cells surviving intraocular N-methyl-D-aspartate or intraocular kainate induced lesions were retrogradely labeled with horseradish peroxidase and analyzed using an image analysis system. Control animals were retrogradely labeled after vehicle injection only. Cell counting was performed at 48 sampling points over the entire retina and represented a total area of 1.92 mm2 per retina. RESULTS: Larger cells were more sensitive to kainate than to N-methyl-D-aspartate excitotoxicity; smaller cells more vulnerable to N-methyl-D-aspartate excitotoxicity. Further from the optic nerve, more smaller cells survived kainate administration. After N-methyl-D-aspartate administration, larger cells survived most, noticeably in the central retina. CONCLUSIONS: Our results suggest that loss of retinal ganglion cells after N-methyl-D-aspartate or kainate administration affects distinct populations of retinal ganglion cells, dependent upon soma size and retinal location. The mechanism by which certain classes of cells survive or succumb to such insults has yet to be determined.

An experimental basis for implicating excitotoxicity in glaucomatous optic neuropathy.

Most therapy for glaucoma is directed at the management of the intraocular pressure (IOP). Conventional wisdom holds that excessive pressure within the eye leads to the ganglion cell loss/optic nerve damage seen in this disease. Both glutamate and elevated IOP can selectively damage the retinal ganglion cells in the mammalian eye. We have identified an elevated level of glutamate in the vitreous humor of glaucoma patients (27 microM as compared to 11 microM in the control population). This concentration of glutamate suffices--on its own--to kill retinal ganglion cells. It is plausible that the IOP may represent an initial insult that precipitates the production of excessive glutamate. Therefore, even if glutamate elevation is an epiphenomenon associated with the course of the disease, it may contribute to ganglion cell loss in humans. Lowering the IOP may slow down glutamate production, but if nothing is done to block the toxic effects of glutamate as well, visual loss may result despite excellent IOP control. If interventions can be found to retard the production or toxic effects of glutamate, it may be possible to slow glaucomatous visual loss.