Biomedical subjects

D Felix

Publications and source records attributed to D Felix.

At least 19 recordsLinked to original sources

PubMed2004

Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases.

AIMS: To assess the usefulness of immunohistochemistry in delineating tumour diagnoses on a series of morphologically diagnosed renal spindle cell tumours (RSCTs). METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues from 31 morphologically diagnosed tumours were reinterpreted in light of newly obtained immunohistochemical information. By morphology, six had originally been classified as sarcomatoid carcinoma, five as spindle cell tumour (NOS), four as sarcoma (NOS), three as leiomyoma, three as leiomyosarcoma, and one each as fibrous polyp, hamartoma, neurilemmoma, mesoblastic nephroma, medullary fibroma, angiomyolipoma, haemangiopericytoma, malignant rhabdoid tumour, malignant Triton tumour, and carcinosarcoma. The application of immunohistochemistry verified the original diagnosis in 18 cases (18/31, 58%), confirming the diagnosis of sarcomatoid renal carcinoma (4/6), leiomyoma (2/3), leiomyosarcoma (3/3), sarcoma (NOS) (2/4), carcinosarcoma (1/1), malignant rhabdoid tumour (1/1), malignant Triton tumour (1/1), fibrous polyp (1/1), mesoblastic nephroma (1/1), hamartoma (1/1), and angiomyolipoma (1/1). Different tumour designations were suggested in 13 cases (13/31, 42%), including carcinosarcoma, sarcoma (NOS), leiomyosarcoma, solitary fibrous tumour, monomorphic/biphasic angiomyolipoma, endometrial stromal tumour, and congenital mesoblastic nephroma. CONCLUSIONS: Our data indicate that although morphology is most important in formulating the initial differential diagnosis, the addition of immunohistochemistry is vital in arriving at the correct classification of RSCTs.

Adolescent↗

PubMed2003

The use of sentinel node biopsy in the management of epitheloid haemangioendothelioma of the lip.

This report describes a rare tumour, an epitheloid haemangioendothelioma affecting the lower lip. This tumour has a predilection for the head and neck region in young adults. Its potential to metastasise is well recognised, but the likelihood of this is currently uncertain. Current management is usually to locally excise the tumour and follow up, although there is a recognised risk that subsequent presentation with metastatic nodal disease can occur. We present a case occurring in the lip of an 18-year-old girl who had a sentinel node biopsy performed as a staging tool in conjunction with excision of a local recurrence. Although clinical examination and CT imaging of the head and neck found no evidence of metastatic disease, the sentinel node was found to contain metastatic tumour. The result of this unexpected finding was that she was investigated further with additional CT scanning of her chest and abdomen. Subsequently, a therapeutic modified radical neck dissection preserving the accessory cranial nerve was undertaken. After 3 years she remains well with no evidence of recurrent tumour. We believe that the consequence of undergoing sentinel node biopsy, which detected early metastatic tumour and her subsequent treatment, suggests a role for sentinel node biopsy in the management of epitheloid haemangioendothelioma.

Adolescent↗

PubMed2002

Role of substance P in the peripheral vestibular and auditory system.

The central role of substance P (SP) has attracted growing interest in the past two decades. One of the important physiological functions of SP and other tachykinins is that of a neurotransmitter in primary afferent neurons. Recent immunocytochemical, biochemical and electrophysiological investigations on various neurotransmitters support the hypothesis that SP has a similar function in the vestibular and auditory systems of all mammals including humans. The purpose of this review is to give an overview of the distribution and concomitant physiological functions of this peptide in these sensory systems.

Auditory Cortex↗

PubMed2001

A new angiotensinergic system in the CNS of the rat.

The use of two different polyclonal, affinity-purified, monospecific antibodies to ANG II (called BODE and BODE 1) revealed dissimilar distribution of ANG II immunoreactivity within the rat central nervous system (CNS). The ANG II-like material detected using BODE was concentrated in the neurosecretory hypothalamic nuclei, in the inner layer of the median eminence and in the posterior lobe of the pituitary. In contrast, the BODE 1 antibody did not stain the hypothalamic-neurohypophysial angiotensinergic system, and the staining pattern was much more broadly distributed throughout the CNS. BODE 1 is the first antibody that can be used to verify the locations of endogenous angiotensin and their receptor sites in the CNS. The diverse distribution of the ANG II-like material detected by the two antibodies provides strong evidence for the existence of at least two different angiotensinergic systems in the CNS.

Angiotensin II↗

PubMed2001

Nicorandil can induce severe oral ulceration.

OBJECTIVE: To increase physicians' and dentists' awareness that nicorandil is a potential inducer of severe mouth ulceration. STUDY DESIGN: Nine new cases of ulceration from 3 European countries were included in this study. RESULTS: Oral ulceration developed within 9 months of beginning nicorandil therapy, and ulcers resolved within 1 month of withdrawal of the drug. No lesions developed on other epithelia. CONCLUSIONS: A number of drugs used in the care of patients with cardiovascular disease can cause oral adverse effects. Nicorandil, a new potassium-channel activator used in some countries to treat angina pectoris, precipitates persistent ulcerative stomatitis in some patients.

Adult↗

PubMed2000

Morphological and immunocytochemical characterization of electrophysiologically investigated neurons in the PVN of the rat.

This study was carried out to characterize angiotensin II (ANG II) sensitive neurons in the hypothalamic paraventricular nucleus (PVN) of the rat. An approach was chosen in which a combination of an electrophysiological, a morphological, and an immunocytochemical method was focused on one single neuron. The cell's reaction to an application of ANG II and its specific antagonist Losartan (Dup753) was investigated using the technique of intracellular recording inside 450-microm-thick brain slices. A final injection of a fluorescent dye labelled the neurons. Optical sections were taken through the marked cells by a confocal laser-scanning microscope and made into a three-dimensional cell model on a computer. One-micrometer thin sections were cut from the thick slice at the level of the electrophysiologically characterized and marked cell body for immunocytochemical tests with different antibodies. Our results show an example of such a neuron inside the PVN excited by ANG II. It was possible to block this excitation with the specific ANG II receptor subtype 1 (AT1) antagonist Losartan. The result indicated that the ANG II reaction was mediated by the AT1 receptor subtype. Immunocytochemical studies show that this ANG II-sensitive neuron contains ANG II but no vasopressin. The combination of the results enables us to gain improved information on interactions of peptidergic systems.

Angiotensin II↗

PubMed2000

Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in the cochlea in vivo.

Neurotrophins have traditionally been regarded as slow-acting signals essential for neuronal survival and differentiation. Recent studies with neuronal slices, cultures and nerve ending preparations have shown that neurotrophins generate acute changes in nerve activity. Among the secondary sensory cells are the inner hair cells (IHC) and taste buds, cells which express the neurotrophic factors necessary for the survival of their innervating neurons. If in these cells neurotrophins acutely affect the nerve activity of their afferent neurons, as in the central nervous system (CNS), this may have important functional implications for the corresponding sensory transduction processes. The neurotrophin NT-3 has been reported to be expressed in IHCs. We chose an in vivo application system for the microiontophoretic supply of NT-3 in the subsynaptic region of the IHC. The effect of NT-3 on spontaneous and evoked afferent cochlear nerve activities in adult guinea pig inner ear was studied. We observed that NT-3 rapidly increases the spontaneous and glutamate-evoked firing rate of IHC afferents. Moreover, firing induced by both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were specifically enhanced during the presence of NT-3, a process which was selectively blocked by the tyrosine kinase receptor inhibitor K252a. Because we localized NT-3 mRNA not only in IHCs but also in the spiral ganglion, we propose that similar to other sensory systems, afferent and autocrine neurotrophin activities may be responsible for survival of cochlear neurons. In addition, NT-3 in IHCs may operate as a signal-dependent, intrinsic neuromodulator and/or neuroprotector.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Diagnosis of acromegaly in orofacial pain: two case reports.

Acromegaly is an uncommon condition, with an annual incidence in the UK of three per million. The gradual onset of the clinical features mean that often friends and relatives are unaware of the underlying pathology. In view of the morbidity, and indeed mortality, arising from undiagnosed cases, general dental practitioners and other healthcare workers should routinely take note of systemic as well as intra-oral changes occurring in their patients when seen on review. The association of paraesthesia, anaesthesia and pain with acromegaly is well documented. However, there appear to be few reports linking acromegaly with orofacial pain or dysaesthesia. This paper describes two such cases.

Acromegaly↗

PubMed1999

Hypothalamic accessory nuclei and their relation to the angiotensinergic and vasopressinergic systems.

The existence and colocalization of angiotensin II- and vasopressin-like immunoreactivity in individual magnocellular cell groups of the hypothalamus has been demonstrated by using immunocytochemical methods. These neurosecretory magnocellular groups consist of the paraventricular nucleus and the supraoptic nucleus, as well as different accessory cell groups. The fibers from the neurons of the accessory nuclei project directly to adjacent blood vessels and do not comigrate with the hypothalamo-neurohypophysial fiber pathway. On the basis of these findings it can be concluded that in the hypothalamus two different angiotensinergic and vasopressinergic neurosecretory systems exist: (1) an intrinsic hypothalamic and (2) a hypothalamo-neurohypophysial system. The distribution of the accessory cell groups in the hypothalamus is shown in a 3D reconstruction which includes the connection of these magnocellular nuclei with the vascular system in this area.

Angiotensin II↗

PubMed1999

Metabotropic glutamate receptors group I are involved in cochlear neurotransmission.

All three types of ionotropic glutamate receptors, AMPA, NMDA and kainate, contribute to the neurotransmission between inner hair cells (IHC) and afferent neurons in the mammalian cochlea. We used microiontophoretic techniques to investigate whether metabotropic glutamate receptors group I (mGluR I) are also involved in the transmission of IHC afferents of the guinea pig. The mGluR I agonist DHPG produced an increase in afferent firing, which lasted significantly longer than that of the ionotropic agonists AMPA and NMDA. The activation was reversibly blocked by the mGluR I antagonist AIDA in a dose-dependent manner. AIDA also diminished spontaneous activity, but only slightly affected the AMPA- or NMDA-induced firing rate. Our results suggest that mGluR I are involved in peripheral auditory processing.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Stochastic resonance in cochlear signal transduction.

The use of a stochastic resonance model contributes crucially to our comprehension of the intensity resolution characteristics of the mammalian cochlea. In guinea pigs, as demonstrated by different statistical methods, the temporal distribution of the interspike intervals of the spontaneous activity reflects an intrinsic cochlear white noise process, demanded as basic requirement for manifest stochastic resonance phenomena. Brownian motion of cochlear fluids is discussed as the underlying white noise motor. Following our model, the amount of white noise, adjusted at the level of the stereocilia of the inner hair cells, determines the threshold, dynamic range and intensity discrimination limen of an individual afferent neuron of the mammalian cochlea.

Animals↗

PubMed1999

New approaches for inner ear therapy with glutamate antagonists.

In the mammalian cochlea neurotransmission between inner hair cells and afferent auditory neurons is probably mediated by glutamate or another related excitatory amino acid. Neurotoxicity induced by excessive glutamate release seems to play a crucial role in some pathological conditions of the cochlea, such as ischaemia or noise trauma. Thus, glutamate antagonists may be a new therapeutic strategy for different inner ear diseases. Because of their potential severe side-effects only a few glutamate antagonists have so far been adopted for clinical use. We used microiontophoretic techniques to compare the effects of memantine and caroverine on the glutamatergic transmission of inner hair cells of the guinea pig and tested the possibility of a local administration of memantine to the cochlea with a micropump. Memantine selectively inhibited the NMDA (N-methyl-D-aspartate) stimulated activity while caroverine blocked NMDA as well as AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induced activity of inner hair cell afferents. With a flow rate of 1 microl/h the local administration of memantine via a cochleotomy was succeeded in a reversible blockade of the spontaneous and the NMDA induced firing of inner hair cell afferents. These results suggest that local application to the cochlea could be a feasible way to administer glutamate antagonists in sufficient amounts while avoiding systemic side-effects.

Animals↗

PubMed1998

GABA(A) receptor modulates the activity of inner hair cell afferents in guinea pig cochlea.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is mediated by two main categories of receptors: the GABA(A) and GABA(B) receptor. Recent immunocytochemical and electron microscopical studies revealed the existence of GABA at the efferent olivocochlear innervation of the guinea pig cochlea. In this microiontophoretic study we examined the effect of GABA on spontaneous and glutamate or acetylcholine induced activity of afferent fibres in the dendritic region of inner hair cells. Furthermore, the receptor subtypes being responsible for this GABA action were analysed using specific agonists and antagonists on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) induced activity. The spike activities of the subsynaptic area were recorded in the third or fourth turn of the cochlea of anaesthetised guinea pigs. Application of GABA had little effect on spontaneous activity whereas the glutamate or acetylcholine induced firing rate could be depressed by GABA. AMPA and NMDA induced activity was reduced by the GABA(A) agonist muscimol but not by the GABA(B) agonist baclofen. The GABA(A) antagonist blocked the inhibition of both GABA and the GABA(A) agonist. In contrast, the GABA(B) antagonist saclofen was without effect. These results reveal that GABA reduces the activated firing rate of inner hair cell afferents mediated by the GABA(A) receptor subtype.

Acetylcholine↗

PubMed1998

What makes an automated teller machine usable by blind users?

Fifteen blind and sighted subjects, who featured as a control group for acceptance, were asked for their requirements for automated teller machines (ATMs). Both groups also tested the usability of a partially operational ATM mock-up. This machine was based on an existing cash dispenser, providing natural speech output, different function menus and different key arrangements. Performance and subjective evaluation data of blind and sighted subjects were collected. All blind subjects were able to operate the ATM successfully. The implemented speech output was the main usability factor for them. The different interface designs did not significantly affect performance and subjective evaluation. Nevertheless, design recommendations can be derived from the requirement assessment. The sighted subjects were rather open for design modifications, especially the implementation of speech output. However, there was also a mismatch of the requirements of the two subject groups, mainly concerning the key arrangement.

Adult↗

PubMed1997

Inappropriate retinoic acid receptor-beta expression in oral dysplasias: correlation with acquisition of the immortal phenotype.

Retinoids are useful in the treatment of premalignant oral lesions and in preventing the occurrence of second primary cancers after resection of the initial primary oral cancer, but long-term prognosis is still poor, presumably due to malignant cells escaping retinoid control. Previous work has shown that loss of expression of retinoic acid receptor beta is one of the most consistent molecular changes during oral cancer progression in vivo. In this report we demonstrate, using a novel panel of primary cultures of oral lesions, that loss of retinoic acid receptor beta expression at the dysplasia stage occurs during the transition from senescent to immortal phenotype but may occur independently to the loss of CDKN2A/p16 expression.

Carrier Proteins↗

PubMed1997

Intracellular staining of angiotensin receptors in the PVN and SON of the rat.

Our immunocytochemical results demonstrate the presence of angiotensin AT1 receptors in the cytoplasm and at the cell membrane in paraventricular and supraoptic neurons of the rat hypothalamus. The reaction product had a punctate appearance. We found no staining in the cell nucleus. Similar results were obtained with an anti-idiotypic antibody to angiotensin II.

Animals↗

PubMed1997

Dopamine regulates the glutamatergic inner hair cell activity in guinea pigs.

Recent immunocytochemical and biochemical studies support a possible neurotransmitter function of dopamine (DA) in the efferent olivocochlear innervation of the guinea pig cochlea. However, the physiological role of DA in cochlear neurotransmission remains unknown. In the present study microiontophoretic techniques were used for testing the action of DA as well as D1- and D2-agonists and -antagonists on spontaneous and N-methyl-D-aspartic acid (NMDA)-, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-, kainic acid- or glutamate-induced firing of afferent fibres in the dendritic region of inner hair cells. Subsynaptic spike activities of anaesthetised guinea pigs were recorded after exposing the third or fourth turn of the cochlea for electrode penetration. Application of DA alone had very little effect on the spontaneous afferent firing rate. In contrast, firing induced by NMDA or AMPA could be depressed by additional administration of DA in a dose-dependent manner. A similar reduction of the induced spike activity was seen after co-administration of D1- or D2-agonists. The action of DA on glutamate agonist-induced firing could be blocked by D1- as well as D2-antagonists. These results show that DA can depress the activated firing rate of the afferent fibres and that this action is mediated by both D1- and D2-receptor subtypes.

Afferent Pathways↗

PubMed1996

Temperature and pressure effects during erbium laser stapedotomy.

BACKGROUND AND OBJECTIVES: Laser-assisted stapedotomy has become a well-established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment. STUDY DESIGN/MATERIALS AND METHODS: On an inner ear model, time-resolved pressure measurements and Schlieren optical flash photography were performed during the perforation of the stapes foot plate using an erbium laser at 2.79 microns. The laser radiation was transmitted via an optical zirconium fluoride fiber. The laser-treated foot plates were investigated by light microscopy and scanning electron microscopy to visualise the laser-induced tissue effects. RESULTS: Perforation of the stapes foot plate can be performed with a few erbium laser pulses with high precision and a thermal damage zone of < 10 microns. Strong pressure transients were found to be generated by the bone ablation process and the collapse of a vapor channel created in the perilymph after fenestration. CONCLUSION: From the comparison of the laser-induced pressure with the limit graph to avoid hearing defects published by Pfander, an unobjectionable use of the erbium laser is deduced for fluences < 10 J/cm2. The erbium laser seems to represent an ideal instrument for middle ear surgery with all the advantages (precision, fiber optic transportable, high ablation efficiency, safety) desired for clinical application.

Erbium↗