Zur Ätiologie der myatrophen Spinalerkrankungen

Ohne Zusammenfassung     

Die pathologische Anatomie der Influenza 1918/19

Ohne ZusammenfassungAus dem pathologisch-anatomischen Institut des Allgemeinen Krankenhauses Barmbek. Prosektor Professor Dr. Fahr.Mit 8 Textabbildungen.     

Neoadjuvant therapy for advanced head and neck cancer with allopurinol-modulated high dose 5-fluorouracil and cisplatin. A phase I-II study

The combination of cisplatin (100 mg/m2) and 5-fluorouracil (5-FU) by continuous infusion (1 g/m2/day for 5 days) has been reported to produce a high response rate as neoadjuvant therapy for advanced squamous cell head and neck cancer. We sought to improve the response rate by increasing the dose of 5-FU to 1.5 g/m2/day and 2.0 g/m2/day with allopurinol modulation to reduce toxicity. The overall response rate in the 30 patients who received three courses of chemotherapy was 100% with a 50% complete response (CR) rate. A 50% CR rate was observed in patients with T3 (six of 12) and N3 (four of eight) disease. Six patients (four with CR) did not complete subsequent treatment as planned. Seven of 11 (63.6%) chemotherapy complete responders and three of 12 (25%) partial responders (one lost to follow-up) who received all planned treatment are free of disease. The major toxicity encountered was stomatitis (severe in 32%) followed by leukopenia. The maximum tolerated dose of 5-FU in this combination with allopurinol protection was 1.5 g/m2/day. Cisplatin plus high dose 5-FU does not appear to be associated with a higher CR rate than that reported with conventional doses of 5-FU and is more toxic.     

Long QT syndrome caused by a large duplication in the KCNH2 (HERG) gene undetectable by current polymerase chain reaction-based exon-scanning methodologies

BACKGROUND: The numerous mutations in the long QT syndrome (LQTS)-associated genes reported to date are point mutations or small insertions and deletions in coding regions or at splice junctions. OBJECTIVES: The purpose of this study was to determine the relative copy number of gene exons in a series of mutation-negative LQTS probands. METHODS: We used a quantitative multiplex approach because the polymerase chain reaction (PCR)-based exon-scanning methodologies routinely utilized in mutation analysis are unable to detect large genomic alterations. RESULTS: We identified the first large gene rearrangement consisting of a tandem duplication of 3.7 kb in KCNH2 responsible for LQTS in a Dutch family. This large duplication is expected to lead to nonfunctional or severely debilitated channels, thereby decreasing I(Kr). CONCLUSION: Our findings have implications for genetic testing in the approximately 30% of LQTS patients in whom conventional mutation screening fails to uncover a mutation. Analysis for large gene alterations such as the one described herein in routine genetic testing may provide a genetic diagnosis in a number of these patients.     

Über einen Fall von isolierter produktiver Riesenzellen-Myocarditis

Zusammenfassung Es wird über einen Fall von isolierter produktiver Riesenzellen-myocarditis berichtet, der weder zur Tuberkulose noch zur Lues gerechnet werden kann, sondern der zu den vonKaufmann beschriebenen Fällen unbekannter Ursache gezählt werden muß.In Heft 5 des 8. Jahrgangs Der deutsche Militärarzt vom Mai 1943 erschien ein Aufsatz vonFischer Über eine eigenartige Form von Myocarditis und die Frage der Wehrdienstbeschädigung, auf den Herr Prof.Merkel mich aufmerksam machte. In dem FallFischer handelt es sich um einen meinem Fall histologisch sehr ähnlichen. Er ist dadurch ausgezeichnet, daß esFischer gelang, den Primärherd, die Eintrittsstelle des unspezifischen Erregers (Kokken), aufzufinden.     

Chemical stability,biological activity and cellular uptake of a cisplatin analogue having a 1,2-diarylethyleneamine ligand in cultures of human breast cancer cells

The platinum(II) complex PtCl₂(meso-6), which has the estrogenic ligandmeso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine (meso-6), has been reported to be an effective antitumor drug for estrogen-receptor(ER)-positive tumors in animal experiments. The goal of this study was to investigate whether the observed biological effects could be ascribed to the intact PtCl₂(meso-6). Cultures of the ER-positive human breast cancer cell line MCF-7 were used as the in vitro test system. In culture medium containing 10% fetal calf serum, PtCl₂(meso-6) had a half-life of about 2 h, as determined by HPLC analysis, and no PtCl₂(meso-6) was detectable after 10 h. The Pt complex bound irreversibly to serum protein. After 30 min, the diamine ligand was found released, with a maximum conversion of about 35% at 24 h. At this time the culture medium still had estrogenic activity, i. e. it induced ER processing in the MCF-7 cells. This indicates that the estrogenic effect was elicited by the released diamine ligand. In contrast, the growth-inhibitory activity of the medium preincubated with PtCl₂(meso-6) was lost at a rate similar to the rate of loss of PtCl₂(meso-6) from the medium. This accords with the platinum complex being the main cytotoxic entity. When MCF-7 cells were incubated with PtCl₂([³H]meso-6), no free Pt complex could be identified in cellular extracts, and most of the cell-associated radioactivity coeluted with meso-6 in HPLC analysis. After 12 h, only 1.4% of the total cellular platinum was bound to DNA, but no tritium label could be detected. In conclusion, diamine ligand is released from the Pt(II) complex and can account for the estrogenic effects so far ascribed to PtCl₂(meso-6).     

Consequences of introducing geometric GTV to CTV margin expansion in DAHANCA contouring guidelines for head and neck radiotherapy

Background and purpose

Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs.

Intracranial complications of paranasal sinusitis: a combined institutional review

Intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies. The charts of all patients (n = 649) admitted for acute or chronic sinusitis to the University of Minnesota Hospital and to the University of Michigan Medical Center during a 13-year period (1975 to 1988) were retrospectively reviewed to determine the incidence of complications. The clinical presentation, bacteriology, involved sinuses, influencing host factors, white blood cell count on presentation, length of hospitalization, and postinterventional complications are presented. Twenty-four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3.7%. Aggressive medical and semi-emergent surgical intervention are required to prevent excessive morbidity and/or mortality. Intracranial complications included subdural empyema, frontal lobe abscesses, intrahemispheric abscesses, cavernous and superior sagittal sinus thrombosis, and osteomyelitis.