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Biomedical subjects

A Rösler

Publications and source records attributed to A Rösler.

At least 19 recordsLinked to original sources
PubMed2004

Binding N2, N2H2, N2H4, and NH3 to transition-metal sulfur sites: modeling potential intermediates of biological N2 fixation.

In the quest for low-molecular-weight metal sulfur complexes that bind nitrogenase-relevant small molecules and can serve as model complexes for nitrogenase, compounds with the [Ru(PiPr(3))('N(2)Me(2)S(2)')] fragment were found ('N(2)Me(2)S(2)'(2-)=1,2-ethanediamine-N,N'-dimethyl-N,N'-bis(2-benzenethiolate)(2-)). This fragment enabled the synthesis of a first series of chiral metal sulfur complexes, [Ru(L)(PiPr(3))('N(2)Me(2)S(2)')] with L=N(2), N(2)H(2), N(2)H(4), and NH(3), that meet the biological constraint of forming under mild conditions. The reaction of [Ru(NCCH(3))(PiPr(3))('N(2)Me(2)S(2)')] (1) with NH(3) gave the ammonia complex [Ru(NH(3))(PiPr(3))('N(2)Me(2)S(2)')] (4), which readily exchanged NH(3) for N(2) to yield the mononuclear dinitrogen complex [Ru(N(2))(PiPr(3))('N(2)Me(2)S(2)')] (2) in almost quantitative yield. Complex 2, obtained by this new efficient synthesis, was the starting material for the synthesis of dinuclear (R,R)- and (S,S)-[micro-N(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] ((R,R)-/(S,S)-3). (Both 2 and 3 have been reported previously.) The as-yet inexplicable behavior of complex 3 to form also the R,S isomer in solution has been revealed by DFT calculations and (2)D NMR spectroscopy studies. The reaction of 1 or 2 with anhydrous hydrazine yielded the hydrazine complex [Ru(N(2)H(4))(PiPr(3))('N(2)Me(2)S(2)')] (6), which is a highly reactive intermediate. Disproportionation of 6 resulted in the formation of mononuclear diazene complexes, the ammonia complex 4, and finally the dinuclear diazene complex [micro-N(2)H(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] (5). Dinuclear complex 5 could also be obtained directly in an independent synthesis from 1 and N(2)H(2), which was generated in situ by acidolysis of K(2)N(2)(CO(2))(2). Treatment of 6 with CH(2)Cl(2), however, formed a chloromethylated diazene species [[Ru(PiPr(3))('N(2)Me(2)S(2)')]-micro-N(2)H(2)[Ru(Cl)('N(2)Me(2)S(2)CH(2)Cl')]] (9) ('N(2)Me(2)S(2)CH(2)Cl'(2-) =1,2-ethanediamine-N,N'-dimethyl-N-(2-benzenethiolate)(1-)-N'-(2-benzenechloromethylthioether)(1-)]. The molecular structures of 4, 5, and 9 were determined by X-ray crystal structure analysis, and the labile N(2)H(4) complex 6 was characterized by NMR spectroscopy.

Journal Article↗
PubMed2004

The fuzzy frontier between subjective memory complaints and early dementia. A survey of patient management in German memory clinics.

BACKGROUND: Mild cognitive decline is frequent in the elderly population. Whether it is related to normal aging or an early phase of evolving dementia is difficult to ascertain with confidence, and accordingly there is a lack of consensus guidelines for diagnosis and therapy in such patients. We assessed the variability with which memory clinics deal with this problem in everyday practice. METHODS: We sent three fictitious case histories to all 85 German memory clinics that contained the results of clinical examination and neuropsychological test scores and asked for diagnosis and patient management. Patient 1 presented with complaints of mental decline but normal neuropsychological and neurological evaluation and normal daily living activities. Patient 2 came in as a control subject for a study and had impaired test scores but preserved daily living activities, and patient 3 was brought in by relatives with slight impairment of daily living activities and decline in some neuropsychological test scores but relatively spared memory scores. RESULTS: Most of the 51 respondents agreed in recommending further neuropsychological testing, a basic laboratory work-up, brain imaging, and a re-examination after 3-6 months. Yet, there was a high variability in the diagnostic terms used, in the additional diagnostic procedures proposed, and in the recommendations concerning therapeutic intervention and driving. CONCLUSIONS: The results reveal a need of practice guidelines for the use of diagnostic terms, therapeutic interventions and driving recommendations in patients between subjective memory complaints and early dementia.

Activities of Daily Living↗
PubMed2003

[Visual search in healthy persons and Alzheimer's patients: relating cognitive function to clinical practice].

Visual search is a complex and highly relevant cognitive task. Hypotheses about the processes involved have been derived from experimental psychology and modified by recent functional imaging methods revealing the underlying neuronal networks. To close the gap between theoretical implications and clinical practice, models of visual search are employed to explain visual search impairments in patients with Alzheimer's disease.

Alzheimer Disease↗
PubMed2002

Idiopathic inflammatory pseudotumor of the orbit and Tolosa-Hunt syndrome--are they the same disease?

Unilateral periorbital pain, cranial nerve palsies and a dramatic response to corticosteroid therapy are the hallmarks of clinical presentation in Tolosa-Hunt-Syndrome (THS) and Idiopathic Pseudotumor of the Orbit (IIPO). Both are unspecific chronic granulomatous diseases of unknown origin, sharing clinical as well as paraclinical characteristics. We observed two patients suffering from acute granulomatous IIPO, who also fulfilled the criteria of THS. Patient 1 developed leftsided infiltration of the medial ocular muscle with periorbital pain and cranial nerve palsy. After an initial response to corticosteroid therapy, contralateral relapse occurred with a THS-like infiltration of the sinus cavernosus and narrowing of the intracavernous internal carotid artery. Granulomatous infiltration of the right sinus cavernosus with secondary involvement of the ipsilateral nervus opticus and a slight exophthalmos was seen in Case 2. According to the literature, MRI and CT show identical signal intensity with different localisation: IIPO preferentially intra- and THS retroorbital. Apart from neuroradiological findings, almost similar histopathology and clinical presentation makes it difficult to distinguish between these two syndromes. Similarities between these two syndromes have been discussed for more than 20 years. Our two cases show their close relationship and we suggest that both diseases belong to the same pathological process.

Adult↗
PubMed2002

Central hyperacusis with phonophobia in multiple sclerosis.

Hearing disorders are a well-described symptom in patients with multiple sclerosis (MS). Unilateral or bilateral hyperacusis or deafness in patients with normal sound audiometry is often attributed to demyelinating lesions in the central auditory pathway. Less known in MS is a central phonophobia, whereby acoustic stimuli provoke unpleasant and painful paresthesia and lead to the corresponding avoidance behaviour. In our comparison collective, patient 1 described acute shooting pain attacks in his right cheek each time set off by the ringing of the telephone. Patient 2 complained of intensified, unbearable noise sensations when hearing nonlanguage acoustic stimuli. Patient 3 noticed hearing unpleasant echoes and disorders of the directional hearing. All patients had a clinical brainstem syndrome. ENT inspection, sound audiometry and stapedius reflex were normal. All three patients had pathologically changed auditory evoked potentials (AEPs) with indications of a brainstem lesion, and in magnetic resonance imaging (MRI) demyelinating lesions in the ipsilateral pons and in the central auditory pathway. The origin we presume in case 1 is an abnormal impulse conduction from the leminiscus lateralis to the central trigeminus pathway and, in the other cases, a disturbance in the central sensory modulation. All patients developed in the further course a clinically definite MS. Having excluded peripheral causes for a hyperacusis, such as, e.g., an idiopathic facial nerve palsy or myasthenia gravis, one should always consider the possibility of MS in a case of central phonophobia. Therapeutic possibilities include the giving of serotonin reuptake inhibitors or acoustic lenses for clearly definable disturbing frequencies.

Adult↗
PubMed2001

Advanced drug delivery devices via self-assembly of amphiphilic block copolymers.

Amphiphilic block copolymers are well established as building blocks for the preparation of micellar drug carriers. Over the past decade, the effectiveness of such self-assembled drug delivery devices has been demonstrated numerous times. This review will discuss two approaches that can be used to further improve the effectiveness of amphiphilic block copolymer-based drug delivery systems. The first approach involves the chemical modification of the block copolymer building blocks. Several examples will be discussed of amphiphilic block copolymers modified with crosslinkable groups in order to increase the stability of the micellar drug carriers, or of block copolymers containing specific ligands that could ultimately allow targeted drug delivery. The second approach to improve the performance of micellar drug carriers is the addition of auxiliary agents. To illustrate this approach, the feasibility of channel proteins and metal (nano)particles to improve temporal control over the drug release process is discussed.

Animals↗
PubMed2001

Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small-vessel disease.

BACKGROUND AND PURPOSE: Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. METHODS: In 16 patients (mean age 68+/-10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. RESULTS: Relative CBFV increase was significantly greater after pravastatin treatment (41.9+/-23.7% versus 55.7+/-18.3%, P=0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences. There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (beta=-0.64, P=0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. CONCLUSIONS: This pilot study provides the first evidence for a significant improvement of cerebral vasomotor reactivity by statin therapy in patients with cerebral small-vessel disease. The results may help to elucidate the preventive effect of statins and provide insights into the pathophysiology of cerebral small-vessel disease.

Acetazolamide↗
PubMed2001

Dynamic allocation of attention in aging and Alzheimer disease: uncoupling of the eye and mind.

CONTEXT: Visual attention can be distributed focally, in the direction of gaze, or globally, throughout the extrapersonal space. Aging, and especially Alzheimer disease (AD), may influence global attention, resulting in shifts of gaze to attend to the global workspace. OBJECTIVE: To determine if subjects who have AD and cognitively intact older subjects shift their gaze more often than young subjects while viewing a dynamic stimulus that emphasizes global attention. DESIGN: Experimental study of eye fixation patterns in response to a simulated driving scene with stationary and moving distractors. SETTING: Urban, medical school, National Institute on Aging-funded Alzheimer's Disease Center. PARTICIPANTS: Thirteen subjects with mild probable AD, 13 age-comparable cognitively intact older control subjects, and 11 young control subjects. MAIN OUTCOME MEASURE: Proportion of eye fixations within and outside of a central region of interest encompassing the "road" surface. RESULTS: Young controls made significantly more eye fixations (mean number of eye fixations, 47.5) than either of the other 2 groups (older controls mean, 33.2; patients with AD mean, 32.2). However, 76% of their fixations remained within the central region of interest. Older controls and subjects with AD made proportionately fewer fixations within this region (48% and 49%, respectively) than young controls and moved their eyes more often to the periphery but did not differ from one another. CONCLUSIONS: Young controls maintain central eye position regardless of peripheral distraction. Older controls move their eyes to the periphery, presumably to widen the window of attention. Subjects with mild AD did not experience an additional disadvantage beyond that associated with aging.

Adult↗
PubMed2001

[Central hyperacusis with phonophobia in multiple sclerosis].

Auditory disturbances are a well known symptom in patients with multiple sclerosis (MS). Uni- or bilateral hypacusis or deafness in patients with normal auditory testing is considered to be a result of lesions in the central auditory pathway. Only rarely described is a central phonophobia whereby acoustic stimuli induce unpleasant and painful perceptions, with consecutive avoidance of these factors. Our first patient described acute shooting pain in the right cheek, triggered only through the ringing of a telephone. The second patient had uncomfortable perception of nonverbal noise. For example the wrinkling of paper bags was unbearable for him. The third patient had difficulties localizing the source of sound and disturbing echos while listening to speech or music. Clinically, in all patients symptoms of a brainstem syndrome were found, whereas auditory testing including inspection, audiometry, and stapedius reflex was normal. We found pathological acoustic evoked potentials (AEP) in all three patients with a prolonged latency III-V and T2 lesions in the ipsilateral pons and central auditory pathway. In case one, we suppose a lateral spread between the lateral lemniscus and the central trigeminal pathway. In the other cases, a dysfunction of the central sensory modulation which controls the regulation of sensitivity of incoming acoustic stimuli seems to be the cause of hyperacusis. All our patients developed clinically confirmed MS in the further course after suffering from phonophobia as their first symptom.

Acoustic Stimulation↗
PubMed2001

[Beyond "successful aging: Rembrandt in his self-portraits].

The process of aging has been generally associated with cognitive dedine. However, some complex cognitive abilities, such as wisdom and judgement, have been suggested to improve with age. In the current study, the development of an advanced artistic ability is examined over the life span of Rembrandt H. van Rijn. Analysis of the paintings revealed the development of an old-age-style in the last portrait, characterised by uniformity of texture, facture, and lighting. The self-portrait painted in the last year of Rembrandt's life reflects a high degree of integration of artistic skill and experience gathered in the course of life, and hence reflects features of wisdom in the sence suggested by Baltes. The development of a mature "late" style can help to characterise the emergence of qualitatively different and advanced cognitive abilities in old age.

Aging↗
PubMed2000

Prospectively randomized comparison of different mechanical aortic valves.

BACKGROUND: The aim of this prospectively randomized study was to evaluate the hemodynamic and functional outcomes after aortic valve replacement with 3 different bileaflet mechanical valves. METHODS AND RESULTS: Three hundred consecutive patients were randomly assigned to receive ATS (n=100), Carbomedics (n=100), or St Jude Medical Hemodynamic Plus (n=100) mechanical aortic valve replacement. There were no significant differences regarding patient age (average 61+/-8 years), body surface area (1.9+/-0.2 m(2)), left ventricular function (ejection fraction 0.59+/-0.17), and presence of aortic stenosis (90%, 89%, and 91%), respectively. All patients had postoperative as well as 6-month and 1-year follow-ups that included transthoracic echocardiography. Multivariate statistical analysis was performed. Implanted valve sizes were comparable at 24+/-2 (ATS), 23.7+/-1.6 (CM), and 23.6+/-1.9 (SJMHP) mm (NS). At 1-year follow-up, the following incidence of events was noted: death 3/1/1, all non-valve related; stroke 0/1/1; trivial transvalvular incompetence 3/3/2; paravalvular leak 2/3/2; and reoperation 0/1/1, respectively (NS). Transvalvular flow velocities were 2.5/2.6/2.4 m/s postoperatively (P:=0.03) and 2.4/2.4/2.3 m/s at 6-month follow-up, respectively (NS). There was a significant decrease in left ventricular mass for all patients but no significant differences among the groups. CONCLUSIONS: There are no clinically relevant differences among the tested bileaflet aortic valves. Regardless of valve type, there was a low complication rate. On the basis of these findings, all 3 bileaflet prostheses are well suited for aortic valve replacement.

Aortic Valve↗
PubMed2000

Pharmacotherapy of paraphilias in the next millennium.

Paraphilias are psychiatric disorders of abnormal sexual behavior whose prevalence has markedly increased during the last decade. Treatment modalities currently used fall into three categories: surgical castration, psychotherapy, and pharmacotherapy. The pharmacological interventions consist of antiandrogens that either completely reduce testosterone secretion and/or antagonize the action of testosterone at the level of the receptor, and psychotropic drugs, namely antidepressants. Cyproterone and medroxyprogesterone acetates are the two antiandrogens more commonly used. They are only effective in relatively high doses, but have a substantial number of severe side effects which has considerably limited their use. Psychotropic drugs may be effective solely in men with a definite obsessive-compulsive disorder component. Because of the erratic results and lack of permanent eradication of the paraphilic manifestations their use in paraphilias is highly controversial. Long-acting gonadotropin-releasing hormone (GnRH) agonist analogues are the most potent antiandrogens, and selectively abolish testosterone secretion in a totally reversible fashion. They are administered parenterally once every 1 to 3 months, and have the fewest side effects. Long-acting GnRH analogues, together with psychotherapy, are highly effective in controlling selected paraphilias (pedophilia, exhibitionism, and voyeurism), and are the most promising mode of therapy in the next millennium. There is an urgent need for good methodological research; carefully designed double-blind controlled studies with a large number of subjects in order to validate or not the use of the various pharmacotherapies.

Drug Therapy↗
PubMed2000

Alterations of visual search strategy in Alzheimer's disease and aging.

Visual search, characterized by eye fixation patterns, was examined in 8 patients with Alzheimer's disease (AD), 8 cognitively intact, age-matched individuals, and 8 young control participants as they searched for a number among a nonlinear array of letters on a large computer screen. Among the 3 groups, target detection accuracy differed and detection time increased linearly. There were more fixations, and fixation duration was significantly longer in the AD patients than in the other 2 groups. These factors contributed to the lengthening of target detection time. This qualitative difference in the architecture of visual search between AD and aging may reflect a specific deficit in the disengagement of visual spatial attention, a prolongation of saccade initiation, or inefficiency in planning a search strategy.

Adult↗
PubMed1998

Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit.

Alterations in the FHIT gene at 3p14.2 occur as early and frequent events in the development of several common human cancers. The ability of human Fhit-negative cells to form tumors in nude mice is suppressed by stable reexpression of Fhit protein. Fhit protein is a diadenosine P1,P3-triphosphate (ApppA) hydrolase whose fungal and animal homologs form a branch of the histidine triad (HIT) superfamily of nucleotide-binding proteins. Because the His-96 --> Asn substitution of Fhit, which retards ApppA hydrolase activity by seven orders of magnitude, did not block tumor-suppressor activity in vivo, we determined whether this mutation affected ApppA binding or particular steps in the ApppA catalytic cycle. Evidence is presented that His-96 --> Asn protein binds ApppA well and forms an enzyme-AMP intermediate extremely poorly, suggesting that Fhit-substrate complexes are the likely signaling form of the enzyme. The cocrystal structure of Fhit bound to Ado-p-CH2-p-ps-Ado (IB2), a nonhydrolyzable ApppA analog, was refined to 3.1 A, and the structure of His-96 --> Asn Fhit with IB2 was refined to 2.6 A, revealing that two ApppA molecules bind per Fhit dimer; identifying two additional adenosine-binding sites on the dimer surface; and illustrating that His-98 is positioned to donate a hydrogen bond to the scissile bridging oxygen of ApppA substrates. The form of Fhit bound to two ApppA substrates would present to the cell a dramatically phosphorylated surface, prominently displaying six phosphate groups and two adenosine moieties in place of a deep cavity lined with histidines, arginines, and glutamines.

Acid Anhydride Hydrolases↗
PubMed1998

Time course of chemokines in the cerebrospinal fluid and serum during herpes simplex type 1 encephalitis.

Chemokines (chemoattractant cytokines) attract and activate specific leukocyte subsets. With regard to their expression by brain parenchymal cells, they may represent the key molecules that control leukocyte entry into the subarachnoid space. In order to evaluate the contribution of chemokines in vivo, we determined the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were drawn by a subarachnoid catheter system throughout the time course of hospitalisation. Results were compared to chemokine levels in serum drawn in parallel. The clinical status was documented by the Modified Barthel Index and correlated with chemokine levels in the CSF. The results were compared with the chemokine levels in the CSF of 17 control patients with normal CSF routine parameters. High chemokine levels were detectable in the CSF of all HSE-patients. MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than those of MCP-1 with a maximum at the time of admission. In all patients the levels of the sIL-2R increased later in the time course, at 14 to 20 h after admission. When the levels of MCP-1 were compared with the clinical status by Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate with the clinical status. Chemokine levels in serum were found to be close to the detection limits of the ELISA systems. Our data suggest that chemokines play an important role in the pathogenesis of HSE. They may be useful parameters to monitor the stage and severity of the disease. The late increase of sIL2-R levels may indicate the beginning of the reconstitution phase.

Cell Count↗