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Biomedical subjects

W Wetzel

Publications and source records attributed to W Wetzel.

At least 19 recordsLinked to original sources
PubMed2006

Allosteric enhancement of metabotropic glutamate receptor 5 function promotes spatial memory.

Group I metabotropic glutamate receptors (mGluRs) have been implicated in learning and memory formation. Recent findings indicate an important function of the group I mGluR subtype 5. Here, we used the Y-maze spatial alternation task and examined whether enhancement of intrinsic mGluR5 activity immediately after learning, i.e. during a critical period for memory consolidation, would have any consequences on long-term memory retention in rats. Intracerebroventricular application of the allosteric mGluR5 potentiator DFB (3,3'-difluorobenzaldazine) resulted in a marked improvement in spatial alternation retention when it was tested 24 h after training. The promnesic effect increased with the difficulty of the task and was apparently due to a substantial enhancement of consolidation. The applied dose of DFB did not cause behavioral changes in the open field, and was devoid of structural side-effects as evaluated by immunohistochemical examination. Our results suggest an important function of post-training mGluR5 activation in some types of hippocampus-dependent spatial learning.

Allosteric Regulation↗
PubMed2004

Interleukin-6: a cytokine to forget.

It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.

Animals↗
PubMed2002

Inhibition of mGluR5 blocks hippocampal LTP in vivo and spatial learning in rats.

Particular subtypes of metabotropic glutamate receptors (mGluRs) have been shown to be specifically involved in certain types of long-term synaptic plasticity and learning. We examined whether inhibition of mGluR5 by the specific noncompetitive antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) has any functional consequences on long-term potentiation in the dentate gyrus in vivo and on learning of a spatial alternation task. Intracerebroventricular application of 13.8 microg MPEP 30 min before tetanization resulted in a rapid decline of potentiation during the first 7 min and a significantly lower potentiation of the MPEP group as compared to controls. The same dose of the antagonist given 30 min before training of a Y-maze spatial alternation task caused a marked impairment of retention tested 24 h later. In contrast, MPEP had virtually no effects on retention if injected immediately after the training session. Our findings suggest an important function of mGluR5 during the initiation of synaptic plasticity and memory formation.

Animals↗
PubMed2001

[Erbium:YAG laser phacoemulsification. Comparison of 2 different application systems].

BACKGROUND: The erbium:YAG laser a suitable energy source for photoablation of several tissues with only minimal thermal side effects. The application system is an important factor in increasing its efficiency. MATERIALS AND METHODS: We used an Er:YAG laser designed for clinical application. The energy was guided via a special coated zirconium fluoride fiber to handpieces of various designs. Twenty lenses of patient eyes were treated using two application systems with 0 degree and 30 degrees tips. RESULTS: Despite similar cataract density an average laser phacoemulsification took significantly less energy and less time using the 0 degree tip. CONCLUSIONS: Use of the Er:YAG laser is superior to ultrasound phacoemulsification in minimizing thermal energy required for lens removal. Certain parameters of the application system construction, in this case the 0 degree tip, can provide additional efficiency. Further developments should pay attention to these findings.

Equipment Design↗
PubMed2000

Clinical and serological aspects of patients with anti-Jo-1 antibodies--an evolving spectrum of disease manifestations.

The aim of this study was to compare ELISA, immunodiffusion and immunoblot for the detection of anti-Jo-1 antibodies, and to investigate the association of the results with clinical manifestations. In two medical centres for rheumatology and one for pulmonology, all patients with suspected connective tissue disease were screened over a 5-year period for anti-Jo-1 antibodies by ELISA. Positive sera were controlled in another laboratory by immunodiffusion. If immunodiffusion was negative, sera were controlled again by ELISA. ELISA-positive immunodiffusion-negative sera were tested by immunoblotting. The patients were characterised clinically, and their clinical signs and symptoms were compared with those of 257 patients with anti-Jo-1 antibodies published in 15 case series and 30 case reports. Twenty-five patients had a positive ELISA test. Fifteen sera were positive by ELISA and immunodiffusion (group 1). Three sera showed high titres in both ELISA tests with negative immunodiffusion and immunoblot (group 2). Seven sera showed low titres in both ELISA tests. The results were negative in the other tests (group 3). Patients in groups 1 and 2 could be classified as Jo-1 syndrome patients. Of these 18 patients, 15 had arthritis, 14 had myositis and 14 had interstitial lung disease. Only four patients had myositis at disease onset. We describe four unusual patients with Jo-1 syndrome in detail: 1. Long history of seronegative rheumatoid arthritis; 2. Sjögren's syndrome with Ro- and La-antibodies; 3. Scleroderma and bronchial carcinoma with centromere antibodies; 4. Corticoid-sensitive psychosis. Patients with suspected connective tissue disease may be screened for anti-Jo-1 antibodies by ELISA. It detects some patients that are missed by immunodiffusion. Especially lower ELISA titres should be controlled by another method because of the low specificity of the test. The clinical picture is variable. Most patients have features other than myositis at disease onset.

Adult↗
PubMed1999

Micronized progesterone: a new option for women's health care.

Although progestational agents have been widely used for gynecologic conditions, treatment options have usually been limited to synthetic agents with adverse effects and sparse patient acceptance. Recent Food and Drug Administration approval of oral micronized progesterone (MP) has introduced therapy with a safe, effective, well-tolerated drug. This article reviews therapeutic indications for MP as illustrated in five case studies. Issues of patient compliance, individualized treatment plans, and patient partnership to obtain the most beneficial outcomes are discussed.

Adult↗
PubMed1998

Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones.

Mongolian gerbils (Meriones unguiculatus) were trained in a shuttle box to discriminate the direction in frequency-modulated tones (FM). Whereas control animals easily acquired FM discrimination, animals with auditory cortex lesion on the right side showed considerable difficulties in learning this task. The discrimination performance of gerbils with left auditory cortex lesion, however, was not different from controls. This study, suggesting that the right auditory cortex plays a dominant role in FM discrimination learning in gerbils, describes a useful animal model for investigation of the basic mechanisms underlying hemispheric asymmetries in auditory perception.

Acoustic Stimulation↗
PubMed1998

Inhibition of group I metabotropic glutamate receptors blocks spatial learning in rats.

Metabotropic glutamate receptors (mGluRs) are postulated to play a role in long-term potentiation and in learning and memory-formation. Previously, we found that the group I/II mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), blocks Y-maze spatial alternation learning. In this study, we tested the group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) in comparison with MCPG using the same behavioural paradigm. Male Wistar rats were intracerebroventricularly injected with either 29 microg 4-CPG or 209 microg MCPG, 30 min prior to learning. Neither 4-CPG nor MCPG had an effect on spatial alternation performance in the training session. In the memory-retention test 24 h later, however, both the 4-CPG- and the MCPG-treated animals were strongly impaired compared with NaCl-injected control rats. These results suggest a particular importance of group I mGluRs in spatial memory-formation and indicate that MCPG effects found in previous learning experiments were predominantly due to an action at group I mGluRs.

Animals↗
PubMed1998

[Ab externo erbium YAG laser sclerostomy versus conventional trabeculectomy. Treatment of glaucoma patients].

PURPOSE: This study was conducted to compare the efficacy of the Er-YAG laser sclerostomy ab externo versus trabeculectomy in the treatment of primary open-angle glaucoma. METHODS: Twelve patients with POAG underwent ab externo laser sclerostomy using an Er-YAG laser (Sklerostom 2.9; lambda = 2940 nm, t = 200 microseconds, 2 Hz, 400 microns, 15 mJ). Only local medication was used, and there were no risk factors for failure. As a control group 12 patients out of 248 standardized trabeculectomies were matched in terms of age, sex, diagnosis and local medications. No antimetabolites were used in either group. RESULTS: After a follow-up of 9 months in the sclerostomy group 53%; (7/12; P = 0.03) showed a patent fistula in comparison of 100% in the trabeculectomy group. There was a significantly lower mean IOP during the first postsurgical week in the group of sclerostomies (3.6 +/- 1.5 mmHg versus 7.5 +/- 2.7 mmHg; P = 0.0001) with a higher incidence of choroidal detachments (9/12 versus 2/12; P = 0.004). The choroidal detachments lasted longer in the sclerostomy group (3.5 months versus 0.3 months; P = 0.014). Iris incarcerations were found only in sclerostomies (7/12; P = 0.05). CONCLUSIONS: Based on these findings, Er-YAG laser sclerostomy prooved to be less effective than trabeculectomy in the treatment of glaucoma patients. Er-YAG laser sclerostomies were associated with a higher incidence of postsurgical complications such as hypotony, choroidal detachments and iris incarcerations. At this point Er-YAG laser sclerostomy is not superior to conventional trabeculectomy.

Aged↗
PubMed1998

Categorical discrimination of direction in frequency-modulated tones by Mongolian gerbils.

Discrimination of the direction of linearly frequency-modulated tones (FMs) was investigated in adult Mongolian gerbils (Meriones unguiculatus) using a footshock motivated shuttle box avoidance go/no go procedure. Symmetric pairs of FMs with frequency linearly increasing with time (ascending FMs) and with frequency linearly decreasing with time (descending FMs) were used as conditioned stimuli, CS+ and CS-, respectively. Stimuli were presented in randomized order in daily sessions over a period of several months. After a number of sessions, the set of conditioned stimuli was changed with respect to frequency range, steepness of modulation and duration. In experiment 1, we observed that gerbils could discriminate between the ascending 2-4 kHz CS+ and the descending 4-2 kHz CS- after a training period of 10-15 days. In experiment 2, we used FM pairs of six other frequency ranges in successive sessions (6-13; 1-2; 13-25; 0.5-1; 3 6; 0.25 0.5 kHz). We found that in the final session the last FM pair (0.25-0.5 kHz) was discriminated already after 3-4 days. Experiment 3 showed that the animals were able to discriminate five of the FM pairs learned in the separate sessions of experiment 2 (i.e. 10 different stimuli) when they were given in randomized order during one training session. In experiment 4, novel FM pairs (not heard before) and familiar FM pairs (trained in experiments 1-3) were presented within one session. It was found that, except for FMs of very short duration and small frequency range, novel FMs were discriminated according to their modulation direction. These results show that Mongolian gerbils are able to discriminate FM tones by modulation direction and, after familiarization with a number of different FM pairs, transfer the ascending-descending concept to stimuli not heard before.

Acoustic Stimulation↗
PubMed1998

Human identical hormones: real people, real problems, real solutions.

Increasing numbers of women are seeking alternative treatments for menopause and other hormone-related gynecologic disorders. Standard agents may provide symptomatic relief but are linked to high side-effect profiles, decreased compliance, and reduced client satisfaction. They also may contribute to other health issues. This report proposes the use of human identical hormones or natural hormone replacement therapy as a holistic alternative to standard therapy. Guidelines for prescribing and client monitoring are presented. It is critical for nurse practitioners to be aware of alternative treatments as they strive to meet client requests in an ever-changing climate in women's health care.

Adult↗
PubMed1997

Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes.

Substances acting upon rapid eye movement (REM) sleep or paradoxical sleep (PS) can affect the number and/or the duration of PS episodes. In the present study, we investigated the effects of the proopiomelanocortin-derived peptide CLIP (corticotropin-like intermediate lobe peptide, ACTH 18-39) and its N-terminal fragments ACTH 18-24 and ACTH 20-24 on the duration of PS episodes in rats. Intracerebroventricular injection of ACTH 20-24 caused a pronounced prolongation of PS episodes (up to 7 min duration, never seen under baseline conditions), whereas ACTH 18-24 acted in a similar way but without reaching statistical significance. We suggest that short N-terminal CLIP fragment(s) may represent endogenous hypnogenic factor(s) involved in the regulation of paradoxical sleep.

Adrenocorticotropic Hormone↗
PubMed1997

Mitomycin-C in laser sclerostomy: benefit and complications.

BACKGROUND AND OBJECTIVE: The authors studied the effect of topical mitomycin-C administration on the maintenance of filter function and intraocular pressure (IOP) following laser sclerostomy. PATIENTS AND METHODS: Twenty-six patients with a presumed high risk of episcleral scarring were treated intraoperatively with topical mitomycin-C (0.5 mg/ml) for 3 to 5 minutes. Their IOPs were monitored for at least 2 years. The IOP data of these patients were compared with the results for 46 patients who underwent the identical procedure without antimetabolite. RESULTS: IOPs below 23 mm Hg were achieved in 70% of the mitomycin-C-treated patients. Compared with the non-mitomycin-C group, the rate and duration of early postoperative hypotony was significantly increased in the mitomycin-C-treated group. CONCLUSION: Mitomycin-C is useful for maintaining successful filter function in patients with unfavorable prognoses. However, severe and persistent hypotony may occur.

Administration, Topical↗
PubMed1996

Comparing the role of metabotropic glutamate receptors in long-term potentiation and in learning and memory.

1. Neuronal plasticity has been suggested to be the physical substrate for changes underlying the expression of memory. One model which has attracted wide attention as a possible candidate of such neuronal plasticity is long-term potentiation (LTP), mainly investigated in the hippocampus of rodents. Moreover, various processes with different time constants may underlie LTP, and these phases show striking correspondence to different phases of memory. 2. Pharmacological evidence strongly implicates that the neurotransmitter glutamate plays a major role in LTP. Although the involvement of ionotropic glutamate receptors has been proven, the role of the newly discovered metabotropic glutamate receptors is still uncertain. 3. Metabotropic glutamate receptors (mGluRs) comprise a whole family with currently eight members grouped into three classes according to their amino acid sequence identity and pharmacological profile. They are G-protein coupled, either positively linked to phospholipase C (class I) or negatively linked to adenylate cyclase (class II and III), and among other effects are known to induce phosphorylation of ionotropic glutamate receptors as well as modulate the excitability of neurons. Finally, they are heterogeneously distributed throughout the brain. 4. In hippocampal slice preparations, mGluRs have been shown to be involved in the induction of LTP in CA1 and dentate gyrus by some investigators, but others have failed to reproduce such experiments, leaving the question: what are the appropriate conditions for mGluR-mediated LTP? 5. In vivo, metabotropic receptor antagonists have been shown to block, and agonists to facilitate, induction and maintenance of LTP, mainly at perforant path/dentate granule cell synapses. As demonstrated in behavioral investigations, mGluRs apparently play an important part in hippocampus-dependent learning paradigms. As in LTP, antagonists block memory formation; in contrast to LTP, agonists also prevent memory formation. In memory recall metabotropic receptors seem to play no role. 6. Based on current information the authors develop models for a role of mGluRs in both LTP and memory formation. Activation of metabotropic receptors plays a particular modulatory role when high frequency stimulation is weak. Strong tetanization may bypass mGluRs by stimulating other systems leading to, at least phenomenologically, similar LTP, Behaviorally, mGluRs possibly set the signal to noise ratio of the hippocampal circuit.

Animals↗
PubMed1996

Internal carotid artery gunshot wounds.

OBJECTIVE: To review a series of patients who sustained internal carotid artery (ICA) gunshot wounds. DESIGN, MATERIALS, AND METHODS: We retrospectively studied the demographics and clinical presentation, angiographic findings, methods of treatment, and outcome of 38 consecutive patients who had ICA injury identified by angiography. RESULTS: Thirty-four of 38 patients were symptomatic with neck hematomas (32 patients), active hemorrhage (12 patients), and/or neurologic deficit (10 patients). Angiography showed active bleeding in 22 patients and occlusion in 16 patients. Twelve patients were treated operatively by ligation (seven patients), repair (four patients), or intracranial/extracranial bypass (one patient). Twenty-six patients were managed nonoperatively either by angioplasty (one patient), embolotherapy (17 patients), or observation alone (eight patients). Percutaneous balloon catheters were also used in three patients for vascular control of the ICA before operative repair or as a method of assessing intracranial collateral circulation. The mortality of 18.4% was largely related to strokes. CONCLUSIONS: Penetration of the ICA is a very severe injury with a high mortality. The major cause of death in this series was related to neurologic damage associated with carotid injury and shock. However, neurologic deficit among the survivors was uncommon and often resulted from emboli. Interventional radiology can play an important role in the management of these wounds and often obviates the need for operative exploration.

Adolescent↗
PubMed1996

Photofragmentation of lens nuclei using the Er: YAG laser: preliminary report of an in vitro study.

The energy of the erbium: YAG laser (2.940-nm wave-length) can be used for minimally traumatic photoablation due to its high absorption at the tissue water and its consequently low penetration depth. Laser sclerostomy ab externo, an application of this principle, has undergone advanced clinical investigation. Another potential application is photofragmentation of the lens for cataract extraction. A laboratory model Er: YAG laser (flashlamp-pumped. 200-microseconds pulse length, 5-Hz repetition frequency) was coupled to a short low-OH quartz fiber (400 microns in diameter). The laser energy was applied by direct contact of the fiber tip to human lenses with very dense cataract. The lenses rested in a small cuvette filled with an aqueous-humor-analogous fluid. The fragmentablation rate was evaluated in relation to the number of pulses and the pulse energy. A laser-triggered flash-photography unit was engaged to visualize the ablation dynamics. We found tissue-ablation rates to range from 4 to 19 micrograms/pulse, depending on the nucleus density and ulse energy. The maximal size of the removed fragments was always below 500 microns. During ablation, rapidly increasing and collapsing cavitation bubbles were photographed at the distal tip of the application fiber. The impact radius of these cavitation effects markedly exceeded the pure penetration depth of laser radiation at a 2.9-microns wavelength. A clinical application of the method should be possible as judged by the results obtained for tissue-ablation rate and fragment size. Cavitation-bubble dynamics seems to be responsible for the high fragmentation efficiency. Special application probes have to be developed to optimize ablation and to prevent inadvertent destruction of the posterior lens capsule by cavitation effects.

Humans↗