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Biomedical subjects

B Hermann

Publications and source records attributed to B Hermann.

At least 19 recordsLinked to original sources

Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography.

Noncontact, depth-resolved, optical probing of retinal response to visual stimulation with a <10-microm spatial resolution, achieved by using functional ultrahigh-resolution optical coherence tomography (fUHROCT), is demonstrated in isolated rabbit retinas. The method takes advantage of the fact that physiological changes in dark-adapted retinas caused by light stimulation can result in local variation of the tissue reflectivity. fUHROCT scans were acquired from isolated retinas synchronously with electrical recordings before, during, and after light stimulation. Pronounced stimulus-related changes in the retinal reflectivity profile were observed in the inner/outer segments of the photoreceptor layer and the plexiform layers. Control experiments (e.g., dark adaptation vs. light stimulation), pharmacological inhibition of photoreceptor function, and synaptic transmission to the inner retina confirmed that the origin of the observed optical changes is the altered physiological state of the retina evoked by the light stimulus. We have demonstrated that fUHROCT allows for simultaneous, noninvasive probing of both retinal morphology and function, which could significantly improve the early diagnosis of various ophthalmic pathologies and could lead to better understanding of pathogenesis.

Animals↗

Cerebellar atrophy in temporal lobe epilepsy affects procedural memory.

The authors examined a cognitive function mediated by the cerebellum, classical eyeblink conditioning, and its relationship to cerebellar volume in healthy controls (n = 59) and temporal lobe epilepsy subjects (n = 77). Controls demonstrated better conditioning, larger cerebellar volumes, and an association between conditioning and cerebellar volume that was not observed in epilepsy patients. These findings provide support for the hypothesis that cerebellar atrophy in epilepsy affects procedural memory.

Acoustic Stimulation↗

Adaptive-optics ultrahigh-resolution optical coherence tomography.

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 microm) and improved transverse resolution (5-10 microm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.

Equipment Design↗

Advances in broad bandwidth light sources for ultrahigh resolution optical coherence tomography.

Novel ultra-broad bandwidth light sources enabling unprecedented sub-2 microm axial resolution over the 400 nm-1700 nm wavelength range have been developed and evaluated with respect to their feasibility for clinical ultrahigh resolution optical coherence tomography (UHR OCT) applications. The state-of-the-art light sources described here include a compact Kerr lens mode locked Ti:sapphire laser (lambdaC = 785 nm, delta lambda = 260 nm, P(out) = 50 mW) and different nonlinear fibre-based light sources with spectral bandwidths (at full width at half maximum) up to 350 nm at lambdaC = 1130 nm and 470 nm at lambdaC = 1375 nm. In vitro UHR OCT imaging is demonstrated at multiple wavelengths in human cancer cells, animal ganglion cells as well as in neuropathologic and ophthalmic biopsies in order to compare and optimize UHR OCT image contrast, resolution and penetration depth.

Animals↗

[Intensity modulated radiotherapy (IMRT) of head and neck tumors. Increased biological effectiveness in high-risk situations by "integrated boost" therapy].

Primary tumors of the paranasal sinuses are rare entities which, because of precarious localization and frequently diffuse propagation into neighbouring cavities and the skull base, pose a significant therapeutic problem. Even after complete surgical resection, local relapses are frequent. Postoperative radiotherapy is therefore usually indicated. Intensity modulated radiotherapy (IMRT) is a new technique that helps creating dose distributions that conform closely to the target volume while maximally sparing the organs at risk. This results in the possibility of applying escalated doses to the target while still keeping the incidence of side effects low. What is especially appealing is the possibility of shaping the dose distribution within the target in such a way that areas with a presumably high tumor cell load receive increased doses, a concept which is best described by the term "integrated boost". We present the case of a patient with a sinunasal carcinoma and describe the implications of the clinical implementation of this technique.

Biopsy↗

Compact, low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography.

A compact, low-cost, prismless Ti:Al2O3 laser with 176-nm bandwidth (FWHM) and 20-mW output power was developed. Ultrahigh-resolution ophthalmic optical coherence tomography (OCT) ex vivo imaging in an animal model with approximately 1.2-microm axial resolution and in vivo imaging in patients with macular pathologies with approximately 3-microm axial resolution were demonstrated. Owing to the pump laser, this light source significantly reduces the cost of broadband OCT systems. Furthermore, the source has great potential for clinical application of spectroscopic and ultrahigh-resolution OCT because of its small footprint (500 mm x 180 mm including the pump laser), user friendliness, stability, and reproducibility.

Aluminum Oxide↗

Compact, broad-bandwidth fiber laser for sub-2-microm axial resolution optical coherence tomography in the 1300-nm wavelength region.

A novel, compact, user friendly fiber laser with a broad emission bandwidth (MenloSystems, lambdac = 1375 nm, deltalambda = 470 nm, Pout = 4 mW) was used to achieve unprecedented sub-2-microm axial resolution optical coherence tomography (OCT) in nontransparent biological tissue in the 1300-nm wavelength region. Fresh human skin and arterial biopsies were imaged ex vivo with approximately 1.4-microm axial and approximately 3-microm lateral resolution and 95-dB sensitivity, demonstrating the great potential for clinical OCT applications of this stable, low-cost, and turn-on-key fiber laser.

Arteries↗

Radiotherapy of the neuroaxis for palliative treatment of leptomeningeal carcinomatosis.

BACKGROUND: Leptomeningeal carcinomatosis occurs in about 5% of solid tumors and may seriously compromise quality of life. Aim of the present study was to evaluate the feasibility of craniospinal irradiation with and without intrathecal chemotherapy and its efficacy with regard to symptom palliation and survival. PATIENTS AND METHODS: 16 patients (mean age 46 years; nine breast cancers, five lung cancers, one renal cell cancer, one tumor of unknown primary site) with leptomeningeal carcinomatosis occurring after a median interval from primary tumor diagnosis of 5 months (0-300 months) received craniospinal irradiation between October 1995 and May 2000. The median total dose was 36 Gy (à 1.6-2.0 Gy). Ten patients were additionally treated with intrathecal methotrexate (15 mg per cycle, 2-8 cycles). RESULTS: Median survival was 12 weeks, 8 weeks after radiotherapy alone, 16 weeks after combined modality treatment. 14 patients died from disease. Eleven patients (68%) experienced regression of their neurological symptoms during or soon after completion of radiotherapy. Seven patients regained their ability to walk, six had pain reduction, three regression of bladder and bowel incontinence. In three patients symptom progression and in two patients no change occurred. Side effects were: myelosuppression (CTC) Grade I: n = 2, Grade II: n = 4, Grade III: n = 4 patients and Grade IV: n = 1. Nine patients had dysphagia, seven mucositis, three suffered from nausea. No late toxicity was observed. CONCLUSION: Craniospinal radiotherapy is feasible and effective for palliative treatment of leptomeningeal carcinomatosis. As far as the small patient number permits any definite conclusions, combined modality treatment seems superior to irradiation alone.

Adult↗

Antidepressants do not modulate estrogen receptor alpha-mediated gene expression.

The estrogen receptor alpha has been shown to be activated both in a ligand-dependent and in a ligand independent fashion. We investigated whether antidepressants may directly activate the estrogen receptor alpha or enhance ligand-dependent or ligand-independent activation of the estrogen receptor alpha. Whereas both ligand-dependent and ligand-independent activation of the estrogen receptor alpha could be demonstrated in transient transfection studies, antidepressants neither directly activated the estrogen receptor alpha nor did they enhance ligand-dependent or ligand-independent activation. Thus, there are differences between the glucocorticoid receptor and the estrogen receptor alpha with regard to ligand-independent activation and action of antidepressants.

Animals↗

Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology.

Besides their binding to cognate intracellular receptors gonadal steroids may also act as functional antagonists at the 5-HT3 receptor. A structure-activity relationship for the actions of a variety of steroids at the 5-HT3 receptor was elaborated that differed considerably from that known for GABA(A) receptors. Steroids appear to interact allosterically with ligand-gated ion channels at the receptor membrane interface. The functional antagonism of gonadal steroids at the 5-HT3 receptor may play a role for the development and course of nausea during pregnancy and of psychiatric disorders. Moreover, we could demonstrate that 3alpha-reduced neuroactive steroids concurrently modulate the GABA(A) receptor and regulate gene expression via the progesterone receptor after intracellular oxidation. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose dependent fashion in male Wister rats. Moreover, progesterone and 3alpha,5alpha-tetrahydroprogesterone produce a benzodiazepine-like sleep EEG profile in rats and humans. In addition, there is a dysequilibrium of such 3alpha-reduced neuroactive steroids during major depression which is corrected by successful treatment with antidepressants. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. First studies in patients with panic disorder suggest that neuroactive steroids may also play a pivotal role in human anxiety. The genomic and non-genomic effects of steroids in the brain contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may constitute a yet unexploited class of drugs.

Animals↗

A Pacinian hyperplasia of the foot.

A case of Pacinian hyperplasia of the right great toe is reported. Pacinian hyperplasia is a rare benign and recently recognized painful lesion composed of an excess of well formed or hyperplastic Pacinian corpuscules, normaly involved in sensory innervation. This lesion that is usually observed in the hand, must be distinguished from nerve tumors harboring onion-bulb structure which are not true well formed Pacinian corpuscules and from Morton neuroma. Pacinian hyperplasia is considered a reactive lesion and not a true neoplasm. To our knowledge, this case is the first described in the foot.

Aged↗

The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions.

This study surveyed the perceptions about and subjective experience of 1023 people with epilepsy in two community-based samples: one from a national postal survey; the other callers to the Epilepsy Foundation. Response to a mail survey was 49%. In comparison with US Census Bureau norms, respondents had received less education, were less likely to be employed or married, and came from lower income households. Complex partial seizures were the most prevalent seizure type, but a convulsion had occurred in 61%. Fifty percent of respondents reported incomplete control of their seizure disorder, although 25% of these had a seizure in the prior year. Thirteen percent had a longest inter-seizure interval of a year or greater, 37% of 3 months, 22% of 1 month, 10% of 1 week and 4% of 1 day. Respondents listed uncertainty and fear of having a seizure as the worst thing about having epilepsy. Lifestyle, school, driving, and employment limits were also listed as major problems. When asked to rank a list of potential problems, cognitive impairment was ranked highest. These data indicate that ongoing medical and psychosocial problems continue for those with epilepsy in the view of those questioned and their families, even in a sample where the majority report good control of their epilepsy.

Adolescent↗

The impact of epilepsy from the patient's perspective II: views about therapy and health care.

A national survey of 1023 people with epilepsy in the US assessed their attitudes about their therapies. Subjects were drawn from responders to a previous national survey of US households or from those who phoned the Epilepsy Foundation. Overall response rate was 49%. Approximately 90% of the respondents were taking medications for their epilepsy. Only 56% were on monotherapy, while 26% were taking two, 6% three, and 2% four medications. Only 68% of respondents were very satisfied with their current seizure medications. When asked to rank five areas of importance regarding their seizure medication, the rank order (highest to lowest) was seizure control, fewer side effects, convenient dosing regimens and cost. Adverse medication events were listed in descending rank order as problems with cognition, energy level, school performance, childbearing, coordination, and sexual function. Inter-individual differences in side effects of concern were listed, suggesting medication choices should be individualized according to potential side effects. Twenty percent of 920 respondents adjusted their medications on their own, by adjusting amount (62%), dosing schedule (31%), or both (3%). Eighty percent of respondents were satisfied with their medical care systems. In this group, 82% had health insurance that covered epilepsy. The large majority (94%) of respondents had seen a neurologist. Subjects expressed dissatisfaction about time limits and lack of accessible information about epilepsy. People with epilepsy are generally satisfied with efforts to treat their disorder, but adverse events are of concern. Many patients requested more information about epilepsy.

Adolescent↗

Pharmacological characterisation of cortical gamma-aminobutyric acid type A (GABAA) receptors in two Wistar rat lines selectively bred for high and low anxiety-related behaviour.

Two Wistar rat lines that have been selectively bred for high-anxiety-related behaviour (HAB) and low-anxiety-related behaviour (LAB) in the elevated plusmaze test may be considered as a genetically prone animal model to study the neurochemical correlates of anxiety-related behaviour. Because there are pronounced differences between the two lines both in baseline levels of open-arm exploration in the elevated plus-maze test and in sensitivity to the anxiolytic effects of 1 mg/kg diazepam, we used these lines to investigate the pharmacology of the benzodiazepine binding site and the GABA binding site of cortical GABAA receptors. No difference in characteristics of flunitrazepam, zolpidem or muscimol binding to cortical GABAA receptors could be detected between the two lines. Although there was an increase in the brain concentration of the anxiolytic neuroactive steroid allopregnanolone, a potent positive allosteric modulator of GABAA receptors, both in HAB and LAB animals after a forced swim stress, allopregnanolone concentrations did not differ between the two lines. Moreover, plasma dehydroepiandrosterone (DHEA) concentrations were similar in HAB and LAB animals. We conclude that anxiety-related behaviour and benzodiazepine sensitivity in these rat lines are likely to be independent of the pharmacology of cortical GABAA receptors.

Animals↗

Po gene expression is modulated by androgens in the sciatic nerve of adult male rats.

The present results show that androgens are able to modulate the Po gene expression in different models. In particular, we have shown that: (1) the messenger for the androgen receptor (AR) is present in the rat sciatic nerve but not in cultured Schwann cells; (2) castration induces a decrease of Po mRNA levels in the sciatic nerve of male rats, which is counteract by the subsequent treatment with dihydrotestosterone (DHT), the 5alpha-reduced metabolite of testosterone; (3) castration is also able to significantly decrease in the sciatic nerve the activity of the enzyme 5alpha-reductase (which converts testosterone into DHT); and (4) DHT is able to stimulate Po gene expression in cultured Schwann cells. These observations seem to indicate that androgens may exert their effect on Po gene expression via indirect mechanisms; modulation of neuronal influences reaching the Schwann cells through the binding of the androgen to the AR present in neurons may be postulated. However, alternative mechanisms may also be taken in consideration. The data presented suggest indeed that androgens might act on Schwann cells via the progesterone receptor (PR) rather than the AR. It has been observed that: (1) the messenger for PR is present in Schwann cells; (2) DHT may activate the transcriptional activity of a PR-responsive gene by binding to the PR; and (3) putative steroid responsive elements have been described in this paper to be present in the Po promoter region.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery.

BACKGROUND: There is preclinical and clinical evidence that plasma concentrations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydroprogesterone; 3 alpha,5 alpha-THP), a neuroactive steroid that is a positive allosteric modulator of the GABAA receptor, are altered in depression and normalize as a result of antidepressant treatment. However, no data are available on the concentrations of 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydrodeoxycorticosterone; 3 alpha,5 alpha-THDOC), another GABA ergic neuroactive steroid, in depression. METHODS: We studied nine depressed patients before and after treatment with various antidepressants and compared them to healthy matched control subjects. Blood samples were quantified by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. RESULTS: Compared to control subjects, plasma concentrations of 3 alpha,5 alpha-THDOC and its precursor 5 alpha-dihydrodeoxycorticosterone (5 alpha-DHDOC) were increased in depressed patients and were not significantly influenced by antidepressant treatment. However, 3 alpha,5 alpha-THP plasma concentrations were decreased in depression and clinically effective antidepressant treatment was accompanied by an increase of 3 alpha,5 alpha-THP concentrations in these patients. CONCLUSIONS: Our results provide the first evidence for a differential alteration in the plasma concentrations of the 3 alpha-reduced neuroactive steroids 3 alpha,5 alpha-THDOC and 3 alpha,5 alpha-THP in major depression, which is only partially reversed by successful antidepressant treatment.

Adult↗

DNA preservation: a microsatellite-DNA study on ancient skeletal remains.

To determine the effect of environmental factors on the preservation of DNA, archeological teeth of approximately similar age but greatly differing site milieu were examined for DNA content. The complex relational system of locational milieu of the samples was reduced to its essential and, at the same time, easily measurable factors. These are temperature, humidity, pH value, the geochemical properties of the soil, the amount of postmortal organic substances and the general degree of microbial infestation in the respective soil. The relative DNA content in the samples was established by determining the rate of successful polymerase chain reaction (PCR) amplifications. Differences in quantity and quality of the results are attributed to the respective prevailing environmental factor or to the respective storage conditions. Dryness, low temperature and absence of microorganisms favors the preservation of DNA. The bioapatite of bones and teeth, like the DNA, are preserved under neutral or slightly alkaline conditions. Brief storage at room temperature does not affect the amount of amplifiable DNA but does affect the reproducibility of the results. Long storage outside a lab freezer reduces the amount and the reproducibility of DNA amplifications in ancient specimens.

Bone and Bones↗

Neuropsychological and behavioral status of children with complex partial seizures.

Neuropsychological and behavioral status were examined in 57 children aged 7 to 16 years with complex partial seizures (CPS) and compared with 27 sibling control children of the same age. Epilepsy had a significant effect on both cognitive and behavioral adjustment measures. Children with CPS had significant impairment across all seven cognitive domains assessed, reflective of a profile of relatively diffuse and generalized cognitive dysfunction. Age at onset of recurrent seizures was the strongest and most consistent predictor of adequacy of cognitive functioning; earlier age at onset was associated with poorer cognitive status. Children with CPS also had more problems compared with sibling control children on measures of social and school competence and internalizing behavior problems, but not externalizing behaviors. Further, frequency of seizure activity in the past year, rather than age at seizure onset, emerged as the strongest predictor of these behavioral difficulties. These findings are discussed in the context of understanding the impact of CPS on cognition and behavioral adjustment, and identifying the contribution of various aspects of the neurodevelopmental course of CPS to these issues.

Achievement↗