Osteosarcoma of the sella

Primary osteosarcoma of the skull is rare. Osteosarcoma arising from the sellar region is extremely uncommon. The case of a 38-year-old man with osteosarcoma of the sella is described, and the literature is reviewed. The patient was treated with surgery followed by aggressive chemotherapy and radiotherapy. Currently he is in remission at 12 months.     

Progression of steroid-associated osteoporosis after heart transplantation

BACKGROUND: Osteoporosis has been recognized as an important side effect of long-term and of pulsed steroid application after heart transplantation. METHODS: In June 1989 a prospective clinical trial was started to study bone demineralization by quantitative computed tomographic scan. All patients received vitamin D and calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council Standard Units subcutaneously per day was administered in 14-day cycles, whereas group II patients (n = 31) received a placebo preparation. Repeat trabecular and cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation. RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months in the calcitonin group. The values for cortical bone density decreased significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart transplantation. Comparable results were obtained in the placebo group. In both groups bone density remained stable thereafter. Intergroup differences were not of statistical significance. CONCLUSIONS: In heart transplant recipients progressive trabecular bone demineralization is limited to the first 3 postoperative months. Thereafter, bone density remained stable. A positive effect of synthetic calcitonin in addition to prophylactic calcium and vitamin D application could not be proved by repeat quantitative computed tomography.     

The steroid profile of a virilizing ovarian tumor.

A case report of a 25-year-old female with a sex cord stromal virilizing ovarian tumor is presented. The pathway of ovarian steroid secretion in this tumor is elucidated with the dominant elements being pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione, and testosterone. The tumor primarily made testosterone (T) with lesser elevations of androstenedione (A), dehydroepiandrosterone (DHEA), and dihydrotestosterone (DHT). Expert pathologic opinions differed whether this neoplasm was a Sertoli-Leydig tumor or a virilizing granulosa tumor; therefore, it was probably a gynandroblastoma. A unilateral salpingo-oophorectomy was performed and the patient promptly resumed normal ovarian function with ovulation.     

Zusammenh?nge zwischen Arbeitst?tigkeit und Ruhestandspl?nen

Zusammenfassung Im Rahmen des Nationalfonds-Projekts «Arbeitstätigkeit und Ruhestandspläne» wurden in einer Erkundungsstudie Auswirkungen der langfristig ausgeübten Arbeitstätigkeit auf die Bildung von Plänen für die Zeit nach der Pensionierung untersucht. Dabei wurden 200 Personen im Alter von 64 Jahren aus der unmittelbaren Produktion in verschiedenen Betrieben der metallverarbeitenden Industrie mit Hilfe von halbstandardisierten Interviews befragt. Die Fragen betrafen im wesentlichen die Bereiche Arbeit, Freizeit und Pläne für die Zeit der bevorstehenden Pensionierung. Es bestand die Annahme, dass für die erfolgreiche Bewältigung der Pensionierungssituation Pläne notwendig und unabdingbare Voraussetzung für die Ausbildung von Plänen der Erwerb und die fortwährende Weiterentwicklung sozialer und kognitiver Handlungskompetenz sind. Es hat sich gezeigt, dass der prozentuale Anteil von Personen ohne oder mit nur unspezifischen Plänen mit abnehmender Grösse des Handlungsspielraums in der Arbeit zunimmt. Die Untersuchung ergab weiter, dass Personen, die ihre kognitive Handlungskompetenz in der Arbeit trainieren konnten, mehr Pläne mit kognitivem Inhalt bilden, als Personen mit kleinem kognitivem Handlungsspielraum in der Arbeit; analog verhält es sich mit der sozialen Handlungskompetenz in der Arbeit.

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Work Activities and retirement plans

In the course of the research project Work Activities and Retirement Plans financed by the National Foundation of Research, a study was made to explore the consequences of longterm working activities on planning of the time of retirement. 200 persons at the age of 64 years, working on shop floor of enterprises in the metal industry were asked about their work, leisure and plans about the approaching retirement. It was hypothesized that plans are necessary for the successful coping of the retirement situation. For the setting up of plans it is required that social and cognitive competence can be acquired and constantly trained. It has been shown that the proportion of persons with none or unspecific plans rises with the span of action getting smaller. Furthermore the study showed that persons who could train their cognitive competence at work set up more plans with cognitive content than persons who could not: the analogical result has been found with the social competence.

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Travail et plans de retraite

Résumé L'étude «Travail et Plans de Retraite» faite dans le cadre d'un projet financé par le Fond National, explorait les conséquences du travail longuement effectué sur la formation des plans pour le temps de la retraite. 200 personnes, à l'âge de 64 ans, travaillant dans la production directe des entreprises de l'industrie des métaux, étaient interrogées par la méthode des interviews demi-standardisés. Les questions concernaient les sujets du travail, du loisir et de la retraite proche. Il était supposé que la formation des plans était nécessaire pour survenir avec succès la situation de la retraite. Prémisse indispensable pour la formation des plans est l'acquisition et le développement permanent de la compétence sociale et cognitive. Il s'est montré que la proportion des personnes sans plans ou avec des plans sans contenu spécifique augmente avec la latitude d'action. De plus, le résultat de l'étude était que des personnes qui pouvaient entraÎner leur compétence cognitive en travail forment plus de plans avec un contenu cognitif que des personnes qui n'en avaient pas l'occasion; ainsi se présente le résultat avec la compétence sociale.

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Nationalfonds-Projekt Nr. 1.656-077, durchgeführt am Lehrstuhl für Arbeits- und Betriebspsychologie der Eidgenössischen Technischen Hochschule in Zürich (Prof. Dr. Eberhard Ulich)     

Effects of various exposure levels of 2-phenylethanol on fetal development and survival in Long-Evans rats

Phenylethanol was given at different levels (432, 43, or 4.3 mg/kg) by gavage to pregnant Long-Evans rats during the "critical period" of organogenesis. Examination of offspring revealed adverse reproductive and teratogenic effects in a dose-related manner. Intrauterine growth retardation occurred at levels of 432 and 4.3 mg/kg. Embryolethality was 18% at 43 mg/kg and 10% at 4.3 mg/kg. Malformations occurred in the following sequence: 100% at 432 mg/kg; 93% at 43 mg/kg, and 50% at 4.3 mg/kg. Noteworthy dose-related teratogenic effects of phenylethanol in offspring manifested themselves in increased incidences of malformed eyes, neural-tube defects, hydronephrosis, and limb defects.     

Comparative effect of heme analogues on hematopoiesis in lymphoproliferative disorders

Anemia is a common characteristic of lymphoproliferative disorders (LPD) and the impairment of blood formation in these disorders is not fully understood. Heme synthesis and the heme degradative enzyme heme oxygenase are critical to hematopoietic differentiation and disturbances may contribute to anemic states. Tin protoporphyrin (SnPP) is a potent inhibitor of heme oxygenase, and has proven to be a useful clinical agent. Bone marrow cells from seven patients with LPD were studied for their in vitro hemopoietic response to growth factors and SnPP. Heme oxygenase mRNA levels were determined by Northern blot analysis of bone marrow samples. Quantitation of hematopoiesis in cultures with erythropoietin or GM-CSF revealed adequate CFU-E, BFU-E and CFU-GM growth by LPD bone marrow. Inclusion of 10 μM SnPP in cultures was found to significantly enhance CFU-E/BFU-E growth by LPD marrows, whereas Zinc protoporphyrin had a marked inhibitory effect. Little or no effect by SnPP was seen on CFU-GM. In contrast, normal bone marrow cultures failed to show an enhanced response to 10 μM SnPP. Analysis of heme oxygenase mRNA levels revealed that LPD marrows had elevated expression of heme oxygenase mRNA as contrasted with normals. Furthermore, measurements revealed that heme oxygenase activity was markedly suppressed by SnPP in the LPD bone marrow cultures. Results lend further support to the importance of heme oxygenase in the differentiation process. Although LPD bone marrow cells may respond to erythropoietin in vitro, in stressed conditions where heme oxygenase is elevated, suppression of heme oxygenase may potentiate the erythropoietic response in this disease.     

Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis.

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.     

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer.

PURPOSE: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval. EXPERIMENTAL DESIGN: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles. RESULTS: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue. CONCLUSIONS: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit.     

Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days.

PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting.