[Diverse effectiveness of the trabectome for different types of glaucoma]. / Unterschiedliche Effekte der Trabektomoperation auf unterschiedliche Glaukomformen.

PURPOSE: Ab interno trabeculotomy using the trabectome device is a intraocular pressure (IOP) decreasing operation by ablation of the trabecular meshwork and the inner wall of Schlemm's channel. This prospective study analyses the effectiveness of the trabectome operation in 122 patients. PATIENTS AND METHODS: The operation was conducted when topical medication was maxed out with the intraocular pressure (IOP) remaining above the desired target range. In addition to the evaluation of the whole study group further analysis concerned the effectiveness of the trabectome in different subclassifications of glaucoma. In some cases the procedure was combined with cataract surgery and subsequently the results were compared to the plain trabectome OP. The results were split into two groups: "complete success" (without postoperative medication) and "qualified success" (with medication). The evaluation was processed for the IOP levels ≤ 21 mmHg, ≤ 18 mmHg, ≤ 15 mmHg und ≤ 12 mmHg. Follow-up dates were 6 and 12 months after surgery. RESULTS: Baseline IOP was 20.15 ± 7.1 mmHg. After 6 months the average IOP of all patients was 16.53 ± 5.89 mmHg, after 12 months the IOP amounted to 15.6 ± 4.45 mmHg. At both follow-ups approximately 90 % of the "complete success" group exhibited an IOP ≤ 18 mmHg. Also at both follow-ups 75 % of the "qualified success" group achieved a range ≤ 18 mmHg - whereas 50 % gained an IOP ≤ 15 mmHg. In secondary glaucoma an IOP decrease of 36 % was achieved. In open-angle glaucomas and those with dysgenetic altered angles the operation evoked a pressure loss of ca. 20 %. The trabectome-only group as well as the group of combined surgery exhibited a significant lowering of IOP. This was accomplished by a significant reduction of eye drops. After surgery nearly half of all patients required none or 1 eye drop at most. CONCLUSION: The trabectome offers a safe and significant lowering of IOP for around 36 % and seems to be very effective in secondary glaucomas. In dysgenetic alterations and open-angle glaucoma a moderate lowering of IOP (ca. 20 %) may be expected. The amount of eye drops can be reduced for about 42 %. After surgery every second patient requires at most 1 eye drop. The technique can be combined with cataract surgery and permits a penetrating operation at a later date.

Enhancement of awareness through feedback does not lead to interlimb transfer of obstacle crossing in virtual reality.

Locomotor skill transfer is an essential feature of motor adaptation and represents the generalization of learned skills. We previously showed that gait adaptation after crossing virtual obstacles did not transfer to the untrained limb and suggested it may be due to missing feedback of performance. This study investigated whether providing feedback and an explicit goal during training would lead to transfer of adaptive skills to the untrained limb. Thirteen young adults crossed 50 virtual obstacles with one (trained) leg. Subsequently, they performed 50 trials with their other (transfer) leg upon notice about the side change. Visual feedback about crossing performance (toe clearance) was provided using a color scale. In addition, joint angles of the ankle, knee, and hip were calculated for the crossing legs. Toe clearance decreased with repeated obstacle crossing from 7.8 ± 2.7 cm to 4.6 ± 1.7 cm for the trained leg and from 6.8 ± 3.0 cm to 4.4 ± 2.0 cm (p < 0.05) for the transfer leg with similar adaptation rates between limbs. Toe clearance was significantly higher for the first trials of the transfer leg compared to the last trials of the training leg (p < 0.05). Furthermore, statistical parametric mapping revealed similar joint kinematics for trained and transfer legs in the initial training trials but differed in knee and hip joints when comparing the last trials of the trained leg with the first trials of the transfer leg. We concluded that locomotor skills acquired during a virtual obstacle crossing task are limb-specific and that enhanced awareness does not seem to improve interlimb transfer.

Differences in motor response to stability perturbations limit fall-resisting skill transfer.

This study investigated transfer of improvements in stability recovery performance to novel perturbations. Thirty adults (20-53 yr) were assigned equally to three treadmill walking groups: groups exposed to eight trip perturbations of either low or high magnitude and a third control group that walked unperturbed. Following treadmill walking, participants were exposed to stability loss from a forward-inclined position (lean-and-release) and an overground trip. Lower limb joint kinematics for the swing phase of recovery steps was compared for the three tasks using statistical parametric mapping and recovery performance was analysed by margin of stability and base of support. The perturbation groups improved stability (greater margin of stability) over the eight gait perturbations. There was no group effect for stability recovery in lean-and-release. For the overground trip, both perturbation groups showed similar enhanced stability recovery (margin of stability and base of support) compared to controls. Differences in joint angle kinematics between treadmill-perturbation and lean-and-release were more prolonged and greater than between the two gait perturbation tasks. This study indicates that: (i) practising stability control enhances human resilience to novel perturbations; (ii) enhancement is not necessarily dependent on perturbation magnitude; (iii) differences in motor response patterns between tasks may limit transfer.

Evidence that ageing does not influence the uniformity of the muscle-tendon unit adaptation in master sprinters.

Differences in the adaptation processes between muscle and tendon in response to mechanical loading can lead to non-uniform mechanical properties within the muscle-tendon unit (MTU), potentially increasing injury risk. The current study analysed the mechanical properties of the triceps surae (TS) MTU in 10 young (YS; 22 ± 3 yrs) and 10 older (OS; age 65 ± 8 yrs; i.e. master) (inter)national level sprinters and 11 young recreationally active adults (YC; 23 ± 3 yrs) to detect possible non-uniformities in muscle and tendon adaptation due to habitual mechanical loading and ageing. Triceps surae muscle strength, tendon stiffness and maximal tendon strain were assessed in both legs during maximal voluntary isometric plantarflexion contractions via dynamometry and ultrasonography. Irrespective of the leg, OS and YC in comparison to YS demonstrated significantly (P < 0.05) lower TS muscle strength and tendon stiffness, with no differences between OS and YC. Furthermore, no group differences were detected in the maximal tendon strain (average of both legs: OS 3.7 ± 0.8%, YC 4.4 ± 0.8% and YS 4.3 ± 0.9%) as well as in the inter-limb symmetry indexes in muscle strength, tendon stiffness and maximal tendon strain (range across groups: -5.8 to 4.9%; negative value reflects higher value for the non-preferred leg). Thus, the findings provide no clear evidence for a disruption in the TS MTU uniformity in master sprinters, demonstrating that ageing tendons can maintain their integrity to meet the increased functional demand due to elite sports.

Obstacle avoidance training in virtual environments leads to limb-specific locomotor adaptations but not to interlimb transfer in healthy young adults.

Obstacle avoidance is one of the skills required in coping with challenging situations encountered during walking. This study examined adaptation in gait stability and its interlimb transfer in a virtual obstacle avoidance task. Twelve young adults walked on a treadmill while wearing a virtual reality headset with their body state represented in the virtual environment. At random times, but always at foot touchdown, 50 virtual obstacles of constant size appeared 0.8 m in front of the participant requiring a step over with the right leg. Early, mid and late adaptation phases were investigated by pooling data from trials 1-3, 24-26 and 48-50. One left-leg obstacle appearing after 50 right-leg trials was used to investigate interlimb transfer. Toe clearance and the anteroposterior margin of stability (MoS) at foot touchdown were calculated for the stepping leg. Toe clearance decreased over repeated practice between early and late phases from 0.13 ± 0.05 m to 0.09 ± 0.04 m (mean ± SD, p < 0.05). MoS increased from 0.05 ± 0.02 m to 0.08 ± 0.02 m (p < 0.05) between early and late phases, with no significant differences between mid and late phases. No differences were found in toe clearance and MoS between the practiced right leg for early phase and the single trial of the left leg. Obstacle avoidance during walking in a virtual environment stimulated adaptive gait improvements that were related in a nonlinear manner to practice dose, though such gait adaptations seemed to be limited in their transferability between limbs.

Stability recovery performance in adults over a wide age range: A multicentre reliability analysis using different lean-and-release test protocols.

The ability to effectively increase the base of support is crucial to prevent from falling due to stability disturbances and has been commonly assessed using the forward-directed lean-and-release test. With this multicentre study we examined whether the assessment of stability recovery performance using two different forward lean-and-release test protocols is reliable in adults over a wide age range. Ninety-seven healthy adults (age from 21 to 80 years) were randomly assigned to one out of two lean angle protocols: gradual increase to maximal forward-lean angle (maximal lean angle; n = 43; seven participants were excluded due to marker artefacts) or predefined lean angle (single lean angle; n = 26; 21 participants needed to be excluded due to multiple stepping after release or marker artefacts). Both protocols were repeated after 0.5 h and 48 h to investigate intra- and inter-session reliability. Stability recovery performance was examined using the margin of stability at release (MoSRL) and touchdown (MoSTD) and increase in base of support (BoSTD). Intraclass correlation coefficients (confidence intervals at 95%) for the maximal lean angle and for the single lean angle were respectively 0.93 (0.89-0.96) and 0.94 (0.89-0.97) in MoSRL, 0.85 (0.77-0.91) and 0.67 (0.48-0.82) in MoSTD and 0.88 (0.81-0.93) and 0.80 (0.66-0.90) in BoSTD, with equivalence being revealed for each parameter between all three measurements (p < 0.01). We concluded that the assessment of stability recovery performance parameters in adults over a wide age range with the means of the forward lean-and-release test is reliable, independent of the used lean angle protocol.

A Randomized, Double-Blind, Phase 2 Study of the Effects of the Vaccine Vanutide Cridificar with QS-21 Adjuvant on Immunogenicity, Safety and Amyloid Imaging in Patients with Mild to Moderate Alzheimer's Disease.

BACKGROUND: Vanutide Cridificar (ACC-001), a novel investigational immunotherapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer's disease (AD). OBJECTIVES: To evaluate the immunogenicity, safety and impact of ACC-001 with Quillaja saponaria (QS-21) adjuvant on the reduction of brain fibrillar amyloid burden, assayed by positron emission tomography (PET) imaging, in patients with mild to moderate AD. DESIGN: Randomized, phase 2, interventional study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01284387. PARTICIPANTS: Individuals with mild to moderate Alzheimer's disease (Mini-Mental State Examination scores 18-26; measurable amyloid burden in the expected range, on the screening 18F-florbetapir PET scan; and a Rosen modified Hachinski ischemic score ≤4). INTERVENTION: Participants were randomized to 3 µg or 10 µg ACC-001 (each in combination with 50 µg QS-21) or placebo (without QS-21). MEASUREMENTS: Primary endpoint was the change from baseline to week 104 in cerebral amyloid burden as measured by the global cortical average (GCA) standard value uptake ratio (SUVR) based on the brain 18F-florbetapir PET composite cortical SUVR between each ACC-001+QS-21 dose compared with placebo. Secondary endpoints included safety, immunogenicity and pharmacodynamics. Exploratory endpoints included cognitive and functional efficacy, and health outcome measures. RESULTS: Of 126 randomized patients (placebo: 40; ACC-001 3 µg+QS-21: 43; and ACC-001 10 µg+QS-21: 43), 125 received study treatment; 92 (73%) completed the study. Change in 18F-florbetapir PET GCA SUVR, was not significantly different between either of the two ACC-001+QS-21 treatment groups and placebo (3 µg +QS-21 vs. placebo diff=-0.03, p=0.54; 10 µg +QS-21 vs. placebo diff=-0.08, p=0.07), but the trend was numerically consistent with a dose response. The geometric mean peak anti-Aß IgG titers were slightly higher in the 10 µg than the 3 µg group. The proportion of responders was similar in both dose groups of ACC-001+QS-21. The cerebrospinal fluid (CSF) p-tau changes from baseline in both active treatment groups were not statistically different from placebo, but were numerically consistent with a dose response (3 µg +QS-21 vs. placebo diff=-3.2, p=0.57; 10 µg +QS-21 vs. placebo diff=-7.0, p=0.19). The vMRI showed statistically significant faster treatment-related decrease in brain volume in the 10 µg group but was not significant in the 3 µg group, compared with placebo (3 µg diff =-1.3 mL/year, p=0.50; 10 µg diff=-4.2 mL/year, p=0.02). Measured plasma Aß levels increased in parallel with peak anti-Aß titers after each injection. Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) were more frequent in patients who received ACC-001+QS-21 than placebo (6% vs. 0%) but none were symptomatic. The most common treatment-emergent adverse events in the active groups were injection reactions, and occurred more frequently in the ACC-001+QS-21 groups than the placebo (48% vs 8%), the majority of which were mild and transient. CONCLUSIONS: Primary biomarker efficacy endpoints were not statistically significant in either dose group. The numerical decreases in 18F-florbetapir PET GCA SUVR suggests a dose-related trend for greater reductions in fibrillar amyloid burden in the ACC-001+QS-21 10 µg group compared with placebo. Likewise, while not significant, there was a numerical trend of decreased CSF p-tau levels with ACC-001, possibly consistent with a downstream effect in the ACC-001+QS-21 group. Insufficient antibody titers or quality, insufficient power to detect a difference, or too short duration of follow up may be reasons why a statistically significant response was not observed. Brain volume measures showed faster volume loss in the 10 µg treatment group, similar to the effect seen in few earlier AD immunotherapy trials which may suggest removal of amyloid and resultant decrease in inflammation. No new, unexpected safety signals were detected.

Lipophilic amino alcohols with calcium channel blocking activity.

A series of novel lipophilic amino alcohols, analogs of the anticholinergic drug vesamicol, were evaluated for Ca2+ channel blocking activity. The effects of these drugs on depolarization-induced intracellular free Ca2+ concentration ([Ca2+]i) transients were examined in single NG108-15 cells and dorsal root ganglion (DRG) neurons in culture. [Ca2+] was recorded with the Ca2+ indicator Indo-1 and a dual emission microfluorimeter. Structure-activity studies indicated that features required for Ca2+ channel blocking activity were distinct from those required for anticholinergic activity. In particular, the Ca2+ channel blocking activity was insensitive to the configuration at the chiral center, whereas the anticholinergic activity was clearly enantioselective. One of the most active compounds, 3-(3-bromophenyl)-2-hydroxy-1-[1-(4-phenylpiperidinyl)]propane (2b), was characterized in more detail. This compound inhibited the dihydropyridine-sensitive Ca2+ channel response in NG108-15 cells, evoked by depolarization with 50 mM K+, with an IC50 of 5 microM. Field potential stimulation of DRG neurons elicited [Ca2+]i transients mediated by at least three Ca2+ channel subtypes; compound 2b inhibited the entire Ca2+ channel response with an IC50 of 1 microM. A key element required for Ca2+ channel blocking activity was the presence of an electron withdrawing substituent on the pendant phenyl ring. Modification of the amino alcohol structure may lead to more potent compounds with broad spectrum Ca2+ channel blocking activity. These structures provide a new chemical starting point for the development of Ca2+ antagonists.

Excitotoxic swelling occurs in oxygen and glucose deprived human cortical slices.

The experimental evidence linking glutamate to ischemic neuronal injury is derived from in vitro or in vivo animal stroke models. We, therefore, developed an in vitro preparation to determine whether glutamate contributes to early neuronal swelling in oxygen and glucose deprived (OGD) human neocortical slices. In order to monitor neuronal swelling, we measured extracellular tissue resistance in brain slices by passing constant current pulses through two electrodes and recording the voltage drop between them. We verified that NMDA (30 microM) or OGD induced a rise in tissue resistance in rat neocortical slices. We then examined human neocortical slices from 11 patients undergoing resections for intractable epilepsy. Both the rodent and human neocortical slices swelled within 10 min of OGD. In both, the glutamate antagonist dizocilpine (MK-801) reduced the swelling. In the rats, MK-801 (5 microM) prolonged the latency to onset of neuronal swelling following OGD from 7.6 +/- 0.6 min (mean +/- S.E.M., n = 16) to 17.4 +/- 2.6 min (n = 6; p < 0.01). Other putative neuroprotective agents were much less effective in this paradigm. In the human slices, MK-801 again prolonged the latency to resistance increase from 8.6 +/- 0.4 min (n = 8) to 17.2 +/- 1.7 min (n = 9, p < 0.01). This is the direct demonstration that glutamate receptor activation leads to neuronal swelling in substrate deficient human brain. These results, which are similar to those obtained in the rodent brain slices, help validate the animal slices as appropriate models for the study of OGD in human brain.

Eighth nerve lipoma. Case report.

A case of lipoma of the right eighth cranial nerve in the cerebellopontine angle (CPA) is presented. The patient had a clinical, diagnostic, surgical, and postoperative course similar to that of patients with other small CPA tumors. The literature on this rare CPA tumor is reviewed and discussed.

U.S. involuntary mental health commitment statutes: requirements for persons perceived to be a potential harm to self.

The civil commitment statutes of all 50 states and the District of Columbia were reviewed to determine: (1) What is required for a person who is believed to be at serious and imminent risk of self-harm to be eligible for involuntary hospitalization; and (2) Whether an attempt to involuntarily hospitalize was required or was merely an option when the requirements found in number 1 were met. The analysis revealed that nearly 85% of the jurisdictions require dangerousness to self to be the result of a mental illness, and only two jurisdictions mandate attempts at involuntary commitment if a person is deemed to be an imminent harm to self. These results have implications for practice with individuals who are suicidal.

Can Shneidman's "Ten Commonalities of Suicide" accommodate rational suicide?

Shneidman's (1985) commonly reproduced "Ten Commonalities of Suicide" cannot accommodate rational suicide, as the concept has been defined in recent literature, and therefore are not "commonalities" of all suicides. Quotes from Shneidman describing the "commonalities" are provided and selected items are briefly examined in light of one set of criteria for rational suicide. It is suggested that Shneidman's list, which is inherently biased against allowing for the possibility of rational suicide, be renamed so that its contents will not continue to be inappropriately used as evidence that suicide cannot be rational.

Empirically based criteria for rational suicide: a survey of psychotherapists.

This qualitative study was designed to develop a set of empirically based criteria for rational suicide by asking psychotherapists to define "rational suicide." Data analysis revealed three components of a rational suicide: (1) the presence of an unremittingly hopeless condition (eight examples provided), (2) a suicidal decision made as a free choice, and (3) the presence of an informed decision-making process (five elements listed). It is suggested that the criteria may possibly be used in assessing the rationality of suicidal clients.

Observations on the first year of Oregon's Death with Dignity Act.

Using data from the files of Compassion in Dying, we describe 34 individuals who approached Compassion wanting to use the Death with Dignity Act and who died during the first year of the Act's implementation. Of these 34, 10 died using medication prescribed under the Act. Using first-hand data from the dying individuals, their families, and their health care teams, we provide comparisons between predicted outcomes and actual experiences, discuss important elements of the physician-patient relationship, and describe several averted suicides and homicides. We also review changes in end-of-life care in Oregon and provide recommendations about issues in need of further research.

The first year of the Oregon Death with Dignity Act: responses to the commentators.

This reaction article begins by differentiating the authors' data from the official Oregon Health Division Report on the Death with Dignity Act and then provides comments in response to each of the authors/teams who analyzed the original article. The authors use this opportunity to clear up some apparent misunderstandings, to highlight commonalities, and to emphasize a few fundamental differences of opinion.

Requests for physician-assisted death: guidelines for assessing mental capacity and impaired judgment.

This article fills a need in the theoretical and clinical literature by presenting a set of guidelines for assessing mental capacity and impaired judgment when a person makes a request to have physician-assisted death. Because Oregon is the only state to have a law allowing physician-assisted death, the guidelines are placed within the context of the Oregon Death with Dignity Act. A comprehensive overview of the legal and ethical issues associated with the assessment of capacity precedes the actual guidelines.

Guidelines for assessments: reactions to the commentators.

In this short article, the authors respond to the critiques of the four commentators on the original "Guidelines" article. They highlight areas of agreement and disagreement with the other authors in an effort to move the discussion forward.

Using rational suicide as an intervention to prevent irrational suicide.

This paper sets forth the idea that using the concept of, and criteria for, rational suicide can be a clinically useful intervention even with people who may be irrational in their suicidality. Case examples are used to illustrate ways in which reviewing the criteria may help move a person away from an impulsive decision to suicide.

The impact of an HIV/AIDS training course for baccalaureate nursing students.

This study focuses on the impact of a specialized course to train baccalaureate nursing students to work with individuals with HIV disease. The overall goals of the course were to increase general and specific knowledge while improving beliefs regarding individuals with HIV disease. The course outline included components to increase knowledge in the areas of epidemiology, medical considerations, treatment, ethical and legal issues, and psychosocial issues. Pretests and posttests were given to participants and to a comparison group which had not received educational training. Results indicated the training significantly increased HIV/AIDS knowledge, and participants reported more positive beliefs about individuals with HIV disease.