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.     

The clinical indications for identical pathogenesis of isolated and non-isolated testicular relapses in acute lymphoblastic leukaemia

In the present population-based study, we compared the clinical data of testicular relapses with and without concurrent bone marrow relapse and clinical data of the relapses in other locations among boys with acute lymphoblastic leukaemia (ALL), in order to study the possible evidence of early sequestration and local regulation of leukaemic lymphoblast in the testis of humans. The results suggest that the pathogenesis of isolated testicular relapse (T) and testicular relapse with a concurrent bone marrow relapse (T+BM) is likely to be similar. Isolated and non-isolated testicular relapses appeared late after the achievement of remission (T 34±16 months, T+BM 32±15 months) in ALL compared to relapses in other locations (CNS 23±11 months, BM 25±19 months). The better prognosis after testicular relapses (estimated second event free survival probability, 2-EFS: T 0.63, T+BM 0.32) compared to bone marrow relapse (2-EFS: BM 0.13) further suggests that testicular relapse with a concurrent bone marrow relapse possibly originates from the isolated testicular relapse, and that the isolated testicular relapse is a separate entity and not a manifestation of systemic recurrence. Higher frequencies of isolated and non-isolated testicular relapses (T 9%, T+BM 5%) were observed among boys with onset of ALL in early puberty (10-12y) compared to those among younger (T 4%, T+BM 2%) and older (T 0%, T+BM 0%) boys. The late occurrence, the possible association with hormonal maturation and the good prognosis after testicular relapses suggest a possible local regulation of the residual leukaemic lymphoblast in human testis.     

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.