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Biomedical subjects

H Maier

Publications and source records attributed to H Maier.

At least 109 records · Page 6Linked to original sources

Cellular immune defect caused by postsurgical radiation therapy in patients with head and neck cancer.

The effects of locoregional postoperative radiation therapy (60 Gy on average) on cellular immunity were investigated in 11 patients with squamocellular carcinomas of the oral cavity, pharynx, or larynx. During radiation treatment, the total lymphocyte counts, CD8+ T-lymphocyte count, and especially CD4+ T-lymphocyte count decreased significantly. The mean CD4+ T-lymphocyte counts dropped from an average of 739/microl to 183/microl (p <0.001), and the CD4+/CD8+ quotient also decreased significantly. Not only the lymphocyte counts but also the in vitro lymphocyte stimulation responses to several mitogens decreased, with reductions averaging 10% to 50% of normal responses by the end of radiation therapy. Within 3 to 4 weeks after radiation therapy, the CD4+ T-lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency toward normalization. This study shows that postoperative locoregional radiation therapy in patients with head and neck cancer induces a severe generalized impairment of cellular immunity.

CD4 Lymphocyte Count↗

Relationship between progression of disease and immunoglobulin A-anti-Fab-/F(ab')2 autoantibodies in patients with head and neck cancer.

Patients with malignant tumors of the head and neck often have immune defects. Higher serum immunoglobulin (Ig)A levels were reported in this group of patients. We investigated whether IgA-anti-Fab- or IgA-anti-F(ab')2 autoantibodies, which have been shown to correlate with severe dysfunction of the immune system, also appear in patients with head and neck cancer. Sera of 110 patients with squamous cell carcinoma (SCCHN), eight patients with adenoid cystic carcinoma, and 57 healthy control subjects were tested by enzyme-linked immunosorbent assay for IgA-anti-Fab autoantibody activity. Patients with head and neck cancer showed a higher IgA-anti-Fab activity (optical density (OD) = 399; n = 118) than did healthy control subjects (OD = 84; n = 57; p < 0.0001). An association between stage of disease and IgA-anti-Fab activity could be established in patients with SCCHN. Patients with stage IV disease had a significantly higher IgA-anti-Fab activity (OD = 538; n = 51) than had patients with stage I disease (OD = 283; n = 18; p < 0.05). Patients with stage II (OD = 293; n = 13) or stage III (OD = 379; n = 28) disease had intermediate activity. Also a higher IgA-anti-Fab activity than in healthy control subjects could be shown in the eight patients with adenoid cystic carcinoma (OD = 314; n = 8; p < 0.01). The highest IgA-anti-Fab activity was observed in eight patients with SCCHN who died within 6 months after testing (OD = 1004; n = 8), suggesting an association between autoimmunity and final desintegration of physiologic body functions. The occurrence of IgA-anti-Fab/IgA-anti-F(ab')2 autoantibodies might be interpreted as an aspect of immune deficiency in patients with malignant tumors of the head and neck.

Antibodies, Anti-Idiotypic↗

Cellular 'neurothekeoma': an epithelioid variant of dermatofibroma?

AIMS: Cellular neurothekeoma is a rare benign cutaneous neoplasm with conflicting opinions regarding its histogenetic origin (nerve sheath, smooth muscle, myofibroblasts) as well as its relation to myxoid neurothekeoma (nerve sheath myxoma). The present series describes 15 cases whose clinicopathological features indicate a relationship to dermatofibroma. METHODS AND RESULTS: In this retrospective clinicopathological study, the lesions preferentially occurred in adolescents to young adults on the upper half of the body, often clinically diagnosed as some kind of fibrohistiocytic tissue response. Besides characteristic whorled nests to fascicles of palely eosinophilic epithelioid cells, all lesions showed variable clues pointing to dermatofibroma: acanthosis, ill-defined storiform periphery, peripherally accentuated prominent sclerosis and lymphocytic demarcation/infiltration. Immunohistochemically, all cases were positive with NK1C3 (CD57), KiM1p and proliferating cell nuclear antigen, seven were positive for neurone specific enolase, five for factor XIIIa, six for smooth muscle specific actin and three for E9, an antimetallothionein marker. These findings are similar to those of conventional dermatofibromas, the variability of the profile being best explained by time cycle and function dependent changes. Ultrastructurally, two cases showed microfilaments, attachment plaques, prominent pinocytosis and focal remnants of basal lamina. A careful study of the data and photomicrographs from the literature reveals that in many cases similar conclusions could be reached. Obvious discrepancies are most likely due to the confusion with myxoid neurothekeoma, a well circumscribed, more spindly and myxoid, S100 positive lesion of Schwannian origin. CONCLUSION: The appearance of dermatofibromas is markedly influenced by architectural, e.g. in deep penetrating dermatofibroma, and/or cellular/stromal criteria, e.g. in epithelioid cell histiocytoma or sclerosing dermatofibroma. Cellular neurothekeoma seems to be a variant of dermatofibromas with both architectural and cellular/stromal peculiarities, i.e. plexiform pattern, epithelioid cytology and stromal sclerosis.

Actins↗

[Epidemiology of transmissible spongiform encephalopathies (prion diseases) in Austria].

Between 1969 and 1996, transmissible spongiform encephalopathy was definitely diagnosed by autopsy and/or biopsy in 98 Austrian patients. The yearly incidence increased significantly in past years (1996: 1.41 cases per million inhabitants). This increase likely results from increased awareness in the medical community and effectuation of the diagnostic autopsy. The new variant of Creutzfeldt-Jakob disease (CJD), probably transmitted from bovine spongiform encephalopathy (BSE), has not occurred in Austria. The percentage of patients older than 70 years increased until 1989 and declined slightly thereafter. One patient received a dura mater graft 11 years before death. Another patient had familial CJD with a glutamatelysin mutation on codon 200 of the prion protein (PrP) gene PRNP. One more patient died from Gerstmann-Sträussler-Scheinker disease (GSS), three patients from fatal familial insomnia (FFI). Another patient received intramuscular injections of a purified RNA preparation (Regeneresen) produced from various organs including brain. The age at death symmetrically distributes around a median of 64 years. Two CJD patients were unusually young (27 and 30 years). Most patients (72.7%) died within 6 months of disease. Retrospectively, 81% of patients had clinical diagnostic criteria of probable or possible CJD (52% probably and 29% possible). In 19%, clinical criteria for CJD were not fully met. There is no case clustering with specific professional groups or geographic areas. However, residents of Vienna, or Vienna and Lower Austria, respectively, had CJD diagnosed twice or three times more frequently than the rest of the country, indicating regionally differing qualities of case retrieval.

Adolescent↗

Development of a narrow water-immersion objective for laserinterferometric and electrophysiological applications in cell biology.

Laserinterferometric studies of the micromechanical properties of the organ of Corti using isolated temporal bone preparations are well established. However, there are relatively few measurements under in vivo conditions in the apical region of the cochlea because of its inaccessibility with commonly used techniques. Recently, optical-design programs have become affordable and powerful, so that the development of an optimized optical system is within the budget of physiologists and biophysicists. We describe here the development of a long-range water-immersion objective. To circumvent anatomical constraints, it has a narrow conical tip of taper 22 degrees and diameter 2.4 mm. It is a bright-field reflected-light illumination, achromatic objective with magnification of 25x/infinity, a working distance of 2.180 mm and a numerical aperture of 0.45. Chromatic errors are corrected at 546.1 and 632.8 nm, with emphasis on the latter wavelength which is used by the laser interferometer. The field curvature is relatively flat and a diffraction limitation (Strehl ratio better than 0.8) can be obtained in a field of 0.4 mm diameter. Using this objective, sound-induced vibrations of hair cells and Hensen cells could be recorded without placing a reflector on the target area. In addition, this objective was found to be diffraction-limited in the near infra-red (750-830 nm), with a slightly different working distance (2.186 mm), making it suitable for patch-clamp experiments using infra-red, differential interference contrast.

Animals↗

[In vivo cochleoscopy through the round window].

The overall aim of the present investigation was to develop a technique for endoscopic investigation of the cochlea. In the experiments reported here, the possible effect of the endoscope-called the "cochleoscope"-on the electrophysiology of the cochlea was investigated by recording the cochlear action potential (CAP) threshold tuning curve from (0.1-34 kHz). The dorsolateral bulla of anesthesized guinea pigs (with ketamine 60 mg/kg and Rompun 12 mg/kg) was opened, after which the cochleoscope was introduced under micromanipulator control through the round window membrane. Three cochleoscopes were used and had diameters of 0.29 mm, 0.7 mm and 0.89 mm, respectively, containing 2000, 3000 and 3000 fibers each. Experiments in 7 animals showed that the cochleoscope did not influence CAP thresholds. Although the present resolution of the endoscopes is limited, the basilar membrane can be clearly distinguished from the osseous spiral lamina. It is anticipated that improved resolution will allow the cochleoscope to be used for diagnostic purposes in cases of sensorineural hearing loss.

Animals↗

[Microlight-guided spectrophotometry of the cochlea].

BACKGROUND: Intraoperative measurements of local intracapillary hemoglobin oxygenation of the human cochlea via the round window membrane have been shown to be possible using the Erlangen microlight-guided spectrophotometer. The aim of the present study was to develop a new microlight guide suitable for measurements in the round window niche and to evaluate electrophysiologically the possible impact of the procedure on the cochlea. METHODS: Measurements were made for wavelengths of 450 to 900 nm at a total power of 5.3 mW. The exit diameter of the light guide was 200 microns and the angle used was 20 degrees. The recording depth was about 250 microns. The atraumatic character of the spectrophotometry was demonstrated by monitoring the compound action potential (CAP) threshold tuning curve from 1 to 34 kHz in ketanest-anesthetized guinea pigs. RESULTS: CAP thresholds remained constant (0.3 +/- 3.9 dB SPL) during 3 to 30 min of exposure to the light. CONCLUSIONS: These results suggest that the spectrophotometry may be useful as a new technique for intraoperative monitoring of intracapillary hemoglobin without causing physiological deterioration of the cochlea.

Animals↗

[Occupational exposure to paint, lacquer and solvents, and cancer risk in the area of the upper aero-digestive tract].

So far, only few studies exist that have investigated the influence of occupational exposure to paint and lacquer on the risk of cancer in the upper aerodigestive tract. Based on data from the Heidelberg case control study which enrolled 369 patients with carcinomas of the upper aerodigestive tract and 1476 randomized control subjects, the relative risk of head and neck cancer in patients exposed to paint, lacquer and varnish was analyzed. The relative risk (RR) of squamous cell cancer (after adjustment for possible alcohol and tobacco effects) was significantly increased for the larynx (RR = 2.3) and the oral cavity (RR = 3.6). However, this risk was not increased for the pharynx. Our findings and a critical analysis of the literature provide evidence that chronic exposure to paint, varnish and lacquer is a definite risk factor for cancer of the upper aerodigestive tract. Further studies are required to confirm these findings, and to identify more precisely toxic substances encountered in the workplace.

Carcinoma, Squamous Cell↗

Metallothionein overexpression in human brain tumours.

Metallothioneins (MTs) are metal binding proteins overexpressed in various human neoplasms which are associated with resistance to cytotoxic drugs. A series of 156 archival human brain tumours were investigated immunohistochemically for expression of MTs; these included 10 low-grade gliomas, 44 high-grade gliomas, 98 meningeal tumours (19 classical, 30 atypical, 38 anaplastic meningiomas, and 11 haemangiopericytomas or papillary meningiomas), and 4 other tumours. Low-grade gliomas showed heterogeneous MT expression; 32 high-grade gliomas (72.7%) showed MT expression of more than 25% of tumour cells without statistically significant differences between first operations and recurrent tumours. In 2 glioblastomas, the presence of MT was confirmed by Western blotting. The extent of MT immunoexpression showed a statistically significant inverse relationship to the degree of p53 immunoreactivity. In meningiomas, a tendency to a higher percentage of MT-expressing cells was observed from classical over atypical to anaplastic meningiomas, but these differences were not statistically significant. In conclusion, MT expression is present in a significant portion of, especially malignant, brain tumours and might be involved in their poor response to antineoplastic drugs.

Adult↗

Electrorotation of colloidal particles and cells depends on surface charge.

The importance of surface conductivity to the frequency-dependent polarizability and the rotation of particles in circular electric fields (electrorotation) is emphasized by various theoretical and experimental investigations. Although surface conductivity seems to be naturally related to the ionic double layer, there is rare experimental evidence of a direct relationship. To highlight the role of surface charges in electrorotation, an apparatus was developed with a symmetrical three-electrode arrangement for field frequencies between 25 Hz and 80 MHz. The three-dimensional electrostatic field distribution between the electrodes was evaluated numerically. With this device, rotating, gradient, and homogeneous electric fields of defined precision and homogeneity could be applied to slightly conducting suspensions. Surface properties of monodisperse latex particles (O 9.67 microm), carrying weak acid groups, were characterized by suspension conductometric titration. This procedure determined the amount of carboxyl groups and showed that strong acid groups were missing on the surface of these particles. To obtain the electrophoretic mobility, the spheres were separated by free-flow electrophoresis, and the zeta-potential was calculated from these data. Single-particle rotation experiments on fractions of specified electrophoretic mobility were carried out at frequencies between 25 Hz and 20 MHz. By analyzing the pH dependence of the rotation velocity, it could be shown that the rotation rate is determined by surface charges, both at the peak in rotation rate near the Maxwell-Wagner frequency (MWF) and at low frequencies. The inversion of the rotation direction at the MWF peak for vanishing surface charges was demonstrated. An analytical model for the double layer and dissociation on a charged surface was developed that is valid for low and high zeta-potentials. This model could provide convincing evidence of the linear dependence of the MWF rotation velocity on surface charge.

Colloids↗

Deletion mapping on chromosome 17p in medulloblastoma.

Medulloblastoma is the most frequent paediatric brain tumour. Because of the uniform histology, a common genetic mechanism has been postulated. Loss of heterozygosity (LOH) studies support evidence that a candidate gene, which functions as a tumour-suppressor gene, is located in 17p13. Eighteen tumours were examined for loss of heterozygosity at 15 different loci at chromosome 17p. Nine of 18 (50%) tumours had allelic loss in 17p 13.3-13.2. The smallest region of overlap, which harbours the disease gene, includes markers from UT222 (D17S675) to UT49 (D17S731) and spans a region of less than 6 cM. Candidate genes within this region are HIC-1, a potential tumour-suppressor gene, and DPH2L, a gene that has been cloned from the ovarian critical region. The putative region excludes the p53 gene and the ABR gene, which have been favoured by others. LOH of chromosome 17p may be used as a new prognostic biological marker. Children with an allelic loss had a poorer prognosis than those patients without loss of heterozygosity (P<0.05).

Adolescent↗

[Angioedema of the mucous membranes of the upper aerodigestive tract after administration of ACE inhibitors].

Inhibitors of angiotensin converting enzyme may rarely cause an angioneurotic oedema of the upper aerodigestive tract. The pathomechanism of this side effect depends on an interaction of the drug with hormones regulating the vascular resistance such as the kallikrein kinin system and the prostaglandin system. Anglo-oedema is characterised by subcutaneous or submucosal swelling, which preferably affects the lips, the soft palate, the tongue and the larynx. Pathomechanisms, differential diagnosis and treatment of ACE-inhibitor induced oedema of the upper aerodigestive tract are described by means of 3 case reports.

Airway Obstruction↗

[Chondroma of the petrous bone. A contribution to differential skull base tumor diagnosis].

INTRODUCTION: Cartilaginous tumors of the mid-face and the skull base are rare. CASE REPORT: For the first time, a case report of a chondroma of the base of the ear in a 56-year-old woman is presented. In 1974 the patient developed a facial nerve paralysis while she was pregnant. Twenty-two years later the patient developed persistent headache and CT studies of the head were obtained, which showed an extensive tumorous lesion located at the base of the ear. A tumor was resected through an otoneurosurgical approach. The histological examination showed a chondroma. CONCLUSIONS: Even the rare diagnosis of a chondroma should be considered for a differential diagnosis of skull base tumors.

Chondroma↗

The fixed combination of collagen with components of fibrin adhesive-a new hemostypic agent in skull base procedures.

CSF leak still is one of the major sources of morbidity after extensive skull base procedures. Of the various standard closure techniques of traumatic or iatrogenic dural defects, none provides a really waterlight, persistent closure. Even the supplementary use of fluid fibrin glue did not substantially improve the rate of postoperative CSF leaks. The application of a collagen sheet covered with a fixed layer of solid components of a fibrin tissue glue (TachoComb(R)) overcomes the major drawbacks of dural sealing in skull base surgery. The dural defects of 58 patients undergoing extensive skull base procedures were sealed with this new hemostyptic agent. The series includes 44 patients undergoing primary surgery, 6 patients with traumatic or iatrogenic tears of venous sinuses, and 8 patients with postoperative leaks after previous skull base procedures in which other sealing methods were previously used. In the group of primary surgery, none of the patients had postoperative CSF leakage or venous rebleeding. One patient developed a delayed pneumatocephalus. All cases of patent CSF fistulas were resolved without any adjuvant therapy. Preliminary experience shows that the good sealing and hemostyptic performance of this new agent will considerably reduce the risk of postoperative CSF leak and infection after skull base procedures.

Journal Article↗

Central nervous system pathology in patients with the Guillain-Barré syndrome.

Thirteen autopsy cases of patients with clinical criteria of the Guillain-Barré syndrome were investigated for pathological changes and cellular composition of inflammatory infiltrates in the CNS and PNS. The survival times from the onset of neurological symptoms until death ranged from 1 day to 12 months. In the CNS, degeneration of spinal posterior tracts was seen in three cases. Mononuclear infiltrates consisted of evenly proportioned lymphocytes and macrophages in cases with survival of 1 and 2 days, whereas macrophages predominated in cases with survival of 5 days and longer. Infiltrates presented as nodular clusters around blood vessels and neurons, or were scattered diffusely. They were found within the spinal cord in eight out of 13 cases, within the medulla oblongata in eight out of 12 cases, within the pons in five out of nine cases, and in one out of four midbrains. Activation of microglia, either focal or diffuse, was found in various degrees in 11 out of 13 cases, involving the spinal cord (six out of 13 cases), the medulla oblongata (10 out of 12 cases), the pons (five out of nine cases) or as subependymal rims along the walls of the ventricular system and the central canal of the spinal cord (seven out of 13 cases). In the PNS, myelin loss (12 out of 13 cases), axonal degeneration (six out of 13 cases) and mononuclear cell infiltrates (13 out of 13 cases) were seen in segmental and cranial nerves, spinal ganglia and spinal roots in varying distribution and severity. Mononuclear cell infiltrates were composed of macrophages and T lymphocytes, with even distribution in cases with short survival (1 and 2 days), and predominance of macrophages in cases with protracted clinical course. T lymphocytes were equally composed of OPD4+ and CD8+ cells without obvious differences between cases of short and long duration, or between PNS and CNS infiltrates in 11 out of 12 cases, whilst two cases had a dominant OPD4+ subset. We conclude that CNS pathology is frequent in patients with Guillain-Barré syndrome. It involves axons with secondary myelin impairment, microglial activation and inflammatory infiltration. In this series, primary demyelination is not found in the CNS. Changes such as degeneration of spinal posterior tracts are secondary to pathology in the PNS. Inflammatory cell reactions in the CNS are similar to those in the PNS and to CNS pathology in experimental allergic neuritis. This inflammation might reflect CNS immune activation in the absence of the relevant antigen, in addition to cellular reactions accompanying secondary CNS changes. The presence of distinct pathology in the CNS is in contrast with other recent studies on the pathology of Guillain-Barré syndrome which, unlike this study, may have been influenced by recently introduced treatments.

Adult↗

Proliferation and DNA fragmentation in meningioma subtypes.

Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas. To substantiate this three-step scale of malignancy, we assessed the proliferative activity reflected by Ki-67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas. The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL-2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas. Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P < 0.0001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas. IST indices rose with increasing malignancy and correlated with MIB1 LI (P < 0.0001): they showed a weak inverse correlation with BCL-2 immunoexpression (P = 0.05). BCL-2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis. Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale. (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas.

Antigens, Nuclear↗