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Biomedical subjects

M Hoff

Publications and source records attributed to M Hoff.

At least 19 recordsLinked to original sources

Defective efficacy of retinoic acid treatment in patients with metastatic thyroid carcinoma.

Radioiodine (I-131) therapy is of proven efficacy for differentiated thyroid carcinoma. However, its efficacy relies on specific uptake mechanisms, which may be lost during the evolution of the disease. Attempts to increase the iodine uptake of such tumors have been made using retinoic acid because it exerts redifferentiating effects on thyrocytes. This study aims to assess the capability of the retinoic acid (RA) treatment to reinforce iodine 131-irradiation efficacy for metastatic and progressive multi-irradiated thyroid cancer. In this clinical prospective study, 11 patients (mean age +/- 1 SD = 61 +/- 12 years, sex ratio M/F = 5/6) with a progressive disease despite iterative surgery and iodine irradiations were treated with 13-cis-retinoic acid (1.5 mg/kg day) over 8 weeks prior to I-131 irradiation. The redifferentiating effect of RA was evaluated by serum thyroglobulin (Tg) monitoring during RA treatment and qualitative analysis of iodine uptake on the post-therapeutic whole body scan. The clinical usefulness of RA treatment was assessed by clinical follow-up, Tg monitoring, and tumor size. No serious event that could possibly be related to the treatment was reported. The mean follow up time was 24.2 +/- 12 months (range 3-46 months). Iodine uptake was only slightly improved in two patients. Nevertheless, the clinical benefits of RA seem to be very poor. Five patients died of a metastatic disease. Five others presented new clinical evidences of a progressive disease. In conclusion, this prospective study demonstrates the absence of efficacy of I-131 irradiation combined with RA for the treatment of patients with aggressive, rapidly growing metastatic thyroid cancer. Thus, patients with highly aggressive disease, rapidly growing in a short period from 2 to 6 months, should not be considered for RA therapy.

Adult↗

[Arterial aneurysms as cause of gushing post-tonsillectomy hemorrhage].

Aneurysms of the external carotid artery can be causally for threatening late hemorrhage secondary to tonsillectomy. On the bases of typical, extended and finally dramatic bleeding course in a child the "clinical look" and the sensitivity should be raised for this bleeding cause. Characteristic after apparently inconspicuous post-operative first phase is late signal bleeding with little loss of blood which are replaced after following intervals free of bleeding from bleeding as flood with massive loss of blood. Then vessel-imaging (Angio-MRI or CT) is urgently indicated. By confirmation of the suspicion diagnosis the interventional angiography is the therapy of the choice, although after successful embolisation a fine-meshed postcontrol is necessary, because therapy failures are possible how the described case points. The highest security offers the surgical exploration with aimed vessel stopping.

Aneurysm↗

Molecular cloning and immunological characterisation of potential allergens from the mould Fusarium culmorum.

BACKGROUND: High quality and stability are essential requirements of commercial allergen preparations. Recently we have demonstrated the very low stability of protein allergens in an extract of the ubiquitous mould Fusarium culmorum. OBJECTIVE: The present study was performed to identify, isolate and characterise allergens of F. culmorum as a basis for a stable allergenic reference material. In addition, the significance of IgE binding to carbohydrate structures in the natural allergen source was investigated. METHODS: Sera of 52 subjects with suspected mould allergy were used to determine the IgE binding capacity of a commercial F. culmorum extract and an in-house extract by immunoblotting and enzyme allergo sorbent test (EAST). Binding of IgE-antibodies to putative carbohydrate structures located on glycoproteins was verified by periodate treatment of blot strips prior to immunodetection. A complementary (c)DNA expression library of F. culmorum was prepared and screened for IgE-binding clones using sera from F. culmorum-sensitive individuals. Positive clones were isolated, and the open reading frames were subcloned into expression vectors to produce recombinant proteins in E. coli. The recombinant proteins were tested for their IgE reactivity by immunoblotting and EAST. RESULTS: Using the in-house extract for EAST and immunoblot experiments 44% (23/52) of the sera were found to contain F. culmorum-specific IgE antibodies. Compared to the in-house extract, nearly all IgE-reactivties in the range of 15-30kD were lacking in the commercial preparation as examined by immunoblot analysis and only 10% (5/52) of the sera were found to contain F. culmorum-specific IgE by EAST. IgE binding to putative carbohydrate structures was observed in the high molecular weight range in approximately 50% (12/23) of the IgE-positive sera by both extracts. Three IgE binding clones were isolated from the cDNA-library. One clone (Fus c 1) is homologous to the highly conserved 60S acidic ribosomal protein P2 described as minor allergen in other moulds. The second (Fus c 2) shows high similarity (64%) to a respiratory allergen from the basidiomycete Coprinus comatus (Cop c 2). The third clone (Fus c 3) was not related to known proteins. With sera from 26 individuals sensitised to F. culmorum the IgE prevalence of recombinant proteins rFus c 1, rFus c 2 and rFus c 3 was found to be 35, 50, and 15%, respectively. CONCLUSIONS: F. culmorum may represent an underestimated source of aeroallergens. In contrast to highly labile and poorly standardised F. culmorum extracts, the new recombinant allergens may serve as stable allergenic reference material. A combination of rFus c 1 and rFus c 2 is suitable to diagnose 81% of F. culmorum-sensitised subjects. IgE reactivity to putative carbohydrate structures is relatively frequent, and can not be detected by these allergens.

Allergens↗

Efficacy of superficial and deep regional hyperthermia combined with systemic chemotherapy and radiotherapy in metastatic melanoma.

BACKGROUND AND OBJECTIVE: Response rates of cutaneous-subcutaneous or lymph node metastases of melanoma to systemic chemotherapy are rather low. We report our clinical experience with superficial and deep regional hyperthermia in combination with radiotherapy and/or chemotherapy with carboplatin. PATIENTS/METHODS: We treated 15 patients with metastatic melanoma (6 men, 9 women; age 39-84 years, mean age 60 years) by using superficial or deep regional hyperthermia produced by electromagnetic energy. Superficial hyperthermia was delivered to skin or lymph node metastases in combination with radiochemotherapy in 12 patients, while deep regional hyperthermia was administered with an annular array applicator to lymph node metastases either in combination with radiochemotherapy (1 patient) or with carboplatin alone (2 patients). The clinical response was assessed by clinical evaluation and/or computer tomography and/or ultrasonography at monthly intervals. RESULTS: Both superficial and deep regional hyperthermia was well tolerated. We observed 5 complete local remissions (34%), 6 partial local remissions (40%) and 2 patients with stable disease (13%). The best results were obtained in cutaneous or retroperitoneal metastases. CONCLUSIONS: Local response can be achieved in inoperable metastatic melanoma using superficial or deep regional hyperthermia in combination with radiochemotherapy or chemotherapy.

Aged↗

[Influence of rhinologic usual and unusual drugs on fibroblasts from nasal polyps in cell culture].

BACKGROUND: Nasal polyposis is treated by surgery and/or by medication but in parts without permanent remission. Fibroblasts and their proliferation are involved in the complex mechanism of polyp genesis. Therefore we have analysed the influence of 12 medications on fibroblasts from nasal polyps growing in vitro. METHOD: Nasal polyps, obtained during usual surgical procedure, are enzymatically digested and cultured in serum containing media. The growing cells are identified as fibroblasts using flow cytometry with a AS02-FITC antibody (Dianova). The analysis is achieved with 5 - 6 different fibroblast cultures in each medicament tested, mostly using concentrations of the active substance from 0.006 to 1.333 mg/ml. The fibroblasts are cultured 4 days in the presence of active substances or as controls. Finally the cells are trypsinated and counted. RESULTS: Mometason, Beclomethason, Fluticason, Verapamil and Timolol are the group with the strongest reduction of fibroblasts. Mometason shows a reduction to 6 % of controls at a concentration of 30 micro g/ml whereas the reduction at this concentration amounts to 30 - 60 % in the other members of this group. Mesazalin, Methylprednisolone and Pentoxifylline demonstrate the smallest influence; Prednisolon-21-hydrogen-succinate, Pilocarpin, Piroxicam and Diclofenac show an effect on a middle level. CONCLUSIONS: A strong reduction of fibroblasts from nasal polyps in vitro is possible with usual rhinological medicaments but also with unusual substances in this field.

Administration, Topical↗

[Neuroendocrine tumors of the larynx (NETL)].

UNLABELLED: CASUISTRY: The case of a patient with atypical carcinoid of the larynx is reported and literature about neuroendocrine tumors of the larynx (NETL) is reviewed. BACKGROUND: Especially terminology, histological differentiation, diagnostics and therapy are discussed. CONCLUSIONS: Neuroendocrine tumors are rare and untypically located in the larynx. In spite of this they should to be known as an important differential diagnosis of a laryngeal neoplasia, because of possible malign or highly malign course. The typical localisation of neuroendocrine tumors (NET) are the gastrointestinal tract and the lung, but the clinical course differs from the one of laryngeal manifestation. This means diagnostics and therapy have to be adapted to this special disease. That's why it is important to explore the identity of these tumors scientifically. This is difficult because of the low rate of patients with this disease. The message of this report is the conclusion of the established and appeal for publications of new cases of NETL.

Adult↗

Mutation screening of a neutral amino acid transporter, ASCT1, and its potential role in schizophrenia.

In a previous study, a genome scan of a subset of schizophrenia families from Palau, Micronesia gave evidence suggestive of linkage to microsatellite markers at 2p13-14. In addition, in a large extended multiplex pedigree (K1583), an 11 cM 2p13-14 haplotype segregated with the illness in eight distantly related schizophrenics. The haplotype region includes a neutral amino acid transporter, ASCT1. We mutation-screened the coding region, flanking intronic sequence and 5'-untranslated region of this transporter in affected members of K1583, two Palauan controls and one Caucasian control. Most polymorphisms were found to be silent or common to all samples scanned. A G/A heterozygote within intron 3 was found in one schizophrenic member of K1583, but was not found in any of the other affected members of K1583. A G/A heterozygote within intron 6 was found in two of six schizophrenics tested in K1583, and in one control. As none of the sequence polymorphisms segregated with illness in the eight schizophrenics, it is unlikely that changes in the 5'-untranslated region, coding sequence or flanking intronic sequence of the ASCT gene predispose to schizophrenia in these families.

Amino Acid Transport Systems↗

[Syndromes 19. Fetal alcohol syndrome].

Foetal alcohol syndrome is a syndrome with a rather high incidence. It is characterized by mental retardation, growth deficiency, a striking facial appearance (a.o. short palpebral fissures, short, upturned nose, hypoplastic philtrum, hypoplastic maxilla). Malocclusion and a disturbed facial growth may occur. Mental retardation can interfere with dental treatment.

Child, Preschool↗

[Syndromes 20. Tuberous sclerosis complex].

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disease. It is clinically a very variable disorder. Hamartomas can develop in many different organs, including the skin, kidneys, heart and brain. Diagnosis of patients with minimal expression of the disease can be very difficult. The dentist can contribute to the (early) diagnosis of the disease.

Amelogenesis Imperfecta↗

Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families.

Eight Utah multigenerational families, each with three to six cases of schizophrenia, were phenotyped with two specific measures of inhibitory neurophysiological functioning, P50 auditory sensory gating (P50), and antisaccade ocular motor performance (AS). A genomewide linkage analysis was performed to screen for loci underlying a qualitative phenotype combining the P50 and AS measures. For this composite inhibitory phenotype, the strongest evidence for linkage was to the D22s315 marker on chromosome 22q (lod score = 3.55, theta = 0) under an autosomal dominant model. Simulation analyses indicate that this 3.55 lod score is unlikely to represent a false positive result. Lod scores were 2.0 or greater for markers flanking D22s315. A nonparametric linkage (NPL) analysis of the chromosome 22 data showed evidence for allele sharing over the broad region surrounding D22s315 with a maximum NPL score of 3.83 (p = .002) for all pedigrees combined.

Acoustic Stimulation↗

Invasive ductal carcinoma of the male breast expanding from pacemaker pocket decubitus.

After twenty-five years of therapy with different unifocal pacemaking systems, an 84-year old male patient developed a nonseptic pacemaker decubitus. A rare incidental finding of invasive ductal carcinoma of the right mammary gland was surgically treated by a generous excision of the tumor and by consecutive modified radical mastectomy. According to published literature, the association of invasive ductal carcinoma arising from a pacemaker pocket decubitus and followed by curative treatment has not been previously reported. We do conclude that pacemaker generators in close relationship to the mammary gland should be considered with suspicion.

Aged↗

[Syndromes 16. Osteogenesis imperfecta].

Osteogenesis imperfecta consists of a group of hereditary connective tissue diseases with fragility of the bone as a general feature. Frequently occurring other characteristics are blue sclerae, opalescent teeth, hearing loss, disorders of the skeleton, and hyperextensibility of the joints. Obliteration and the unusual shape of the pulp chambers may interfere with dental treatment.

Humans↗

Evidence for a chromosome 2p13-14 schizophrenia susceptibility locus in families from Palau, Micronesia.

A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning approximately 11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.

Adult↗

Analysis of chromosome 6 markers in eight Utah schizophrenia pedigrees.

Eight multiplex Utah schizophrenia pedigrees were screened for linkage by applying a non-parametric linkage program, GENEHUNTER, using 30 chromosome 6 DNA markers. The overall maximum NPL score of the combined pedigrees was 1.50 (P = 0.079) at marker D6s281, located near the q terminus. The highest overall maximum NPL score for an individual pedigree was 2.81 (P = 0.043). In the chromosome 6p region, where numerous positive findings have been reported, we obtained no positive results.

Chromosomes, Human, Pair 6↗

Immunoradiometric assay of thyroglobulin in patients with differentiated thyroid carcinomas: need for thyroglobulin recovery tests.

As interference from thyroglobulin autoantibodies appears to have been overcome in new commercial thyroglobulin assays by the use of monoclonal antibodies, the need for thyroglobulin recovery tests became uncertain. Sera (n=45) from patients with differentiated thyroid carcinomas were selected on the basis of a thyroglobulin recovery value below 70% in the Dynotest Tg immunoradiometric assay (Brahms) routinely used in our laboratory. Serum thyroglobulin levels were then measured using three other commercial immunoradiometric assays: thyroglobulin ERIA (Pasteur), HTGK (Sorin) and ELSA HTG (Cis Bio International). Thyroglobulin autoantibodies were measured using the Thyrak assay (Brahms). Although many patients were thyroglobulin antibodies-negative (< 200 U/ml, n=26), most immunoradiometric assays failed to detect thyroglobulin in patients with evidence of recurrence. Low thyroglobulin values associated with low thyroglobulin recovery in thyroglobulin antibody-negative patients appear to be more biologically relevant than a single low thyroglobulin value, which can lead to lack of medical intervention. We conclude that the thyroglobulin recovery test is a prerequisite for the correct interpretation of serum thyroglobulin levels determined with immunoradiometric assays in the follow-up of thyroglobulin autoantibody-negative patients treated for differentiated thyroid carcinomas.

Cell Differentiation↗