Pre-irradiation chemotherapy in children with high-grade astrocytoma: Tumor response to two cycles of the ‘8-drugs-in-1-day’ regimen

SummaryPurpose This study was undertaken to evaluate the radiographie response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas.Patients and methods. One hundred and thirty children less than 21 years of age with newly-diagnosed highgrade astrocytoma were treated with the eight-drugs-in-one-day chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist.Results Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p < 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p < 0.001).Conclusion In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.     

Untersuchung zur Kategorisierung des mandibulären Wachstumspotentials von Petrovic,Lavergne und Stutzmann

Zusammenassung In der vorliegenden Studie sollte untersucht werden, ob die vonPetrovic, Lavergne undStutzmann vorgeschlagene Kategorisierung des mandibulären Wachstumspotentials für die Behandlung mit dem Funktionsregler Geltung hat. Dazu wurden die Fernröntgenaufnahmen von 140 Patienten der Angle-Klasse II nach zirka zweijähriger Behandlung mit Funktionsreglern analysiert. Im Vergleich zu 133 unbehandelten Kindern mit Angle-Klasse II trat in fast allen Rotationsgruppen eine signifikant größere Zunahme der Unterkiefergesamtlänge ein. Zwischen der Kategorie 2 mit niedrigem Wachstumpotential und Kategorie 5 mit hohem Wachstumspotential wurden keine signifikant unterschiedlichen Zunahmen der Unterkieferlänge festgestellt.

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Summary The results of the study show whether the classification of mandibular growth potential, as proposed by Petrovic, Lavergne and Stutzmann has any influence on the treatment with a function regulator. X-rays of 140 class II patients were analysed after a treatment time of approximately 2 years. In comparison with 133 class II children without any treatment, a significant increase of the overall mandibular length was observed in almost all children treated. There was no significant difference in the increase of mandibular length between category 2 (low growth potential) and category 5 (high growth potential).

     

Treatment of hypogonadal adolescent boys with long acting subcutaneous testosterone pellets

AIMS: Long acting subcutaneous testosterone pellets are of proved efficacy for the treatment of hypogonadal men, but have not been reported as a treatment modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone release have shown prolonged normalisation of testosterone levels for at least four months. Administration of a long acting, safe, effective, and convenient form of treatment is desirable when life-long treatment is indicated. PATIENTS AND METHODS: Eighteen boys (aged 13.9-17.5 years at the start of treatment)-seven with primary hypogonadism, nine with secondary hypogonadism, and two boys being treated with testosterone for tall stature--were given testosterone pellets (8-10 mg/kg) every six months for 18 months. Height, weight, pubertal status, and psychosocial parameters were assessed and follicle stimulating hormone, luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1, 3, 6, 12, and 18 months. Bone age was measured at 0 and 12 months. RESULTS: In all boys growth velocity continued appropriately for bone age. Puberty continued to progress in all boys and in two boys the amount of virilisation exceeded that seen with previous treatment with intramuscular testosterone. After testosterone administration, follicle stimulating hormone and luteinising hormone suppressed incompletely in the boys with primary hypogonadism. Serum testosterone ranged from 4.3 to 26.7 nmol/l at three months to less than 10 nmol/l at six months after implantation. Prolactin and lipid levels were normal throughout the study. By report, there was an improvement in mood and emotional wellbeing. No pellet extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS: All boys preferred this mode of testosterone administration to intramuscular injections. Long acting subcutaneous testosterone pellets are safe, efficacious, well tolerated, and convenient, and result in normal physical growth and improved psychological outlook in adolescent hypogonadal boys.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Effects of isoflurane, sevoflurane, and halothane on myofilament Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in rat ventricular myocytes

BACKGROUND: The aim of this study was to describe and compare the effects of isoflurane, sevoflurane, and halothane at selected concentrations (i.e., concentrations that led to equivalent depression of the electrically evoked Ca2+ transient) on myofilament Ca2+ sensitivity, sarcoplasmic reticulum (SR) Ca2+ content, and the fraction of SR Ca2+ released during electrical stimulation (fractional release) in rat ventricular myocytes. METHODS: Single rat ventricular myocytes loaded with fura-2 were electrically stimulated at 1 Hz, and the Ca2+ transients and contractions were recorded optically. Cells were exposed to each anesthetic for 1 min. Changes in myofilament Ca2+ sensitivity were assessed by comparing the changes in the Ca2+ transient and contraction during exposure to anesthetic and low Ca2+. SR Ca2+ content was assessed by exposure to 20 mm caffeine. RESULTS: Isoflurane and halothane caused a depression of myofilament Ca2+ sensitivity, unlike sevoflurane, which had no effect on myofilament Ca2+ sensitivity. All three anesthetics decreased the electrically stimulated Ca2+ transient. SR Ca2+ content was reduced by both isoflurane and halothane but was unchanged by sevoflurane. Fractional release was reduced by both isoflurane and sevoflurane, but was unchanged by halothane. CONCLUSIONS: Depressed myofilament Ca2+ sensitivity contributes to the negative inotropic effects of isoflurane and halothane but not sevoflurane. The decrease in the Ca2+ transient is either responsible for or contributory to the negative inotropic effects of all three anesthetics and is either primarily the result of a decrease in fractional release (isoflurane and sevoflurane) or primarily the result of a decrease in SR Ca2+ content (halothane).     

Acquired erythroderma in adults: a clinical and prognostic study

Background Erythroderma is a severe syndrome and prognostic studies are rare in the literature. Objectives Through a retrospective study of erythroderma in adults, we have analysed epidemiological and clinical data and precised the relevant aetiologies and survival in our patients. Methods This study was performed at the Department of Dermatology of Charles Nicolle Hospital of Tunis (1995–2007) including 82 cases of acquired erythroderma (>16 years). We have recorded epidemio‐clinical, biological and histological data, treatment and outcome. Clinical–histological correlation was analysed [kappa coefficient (κ)]. Follow‐up time and disease‐free survival time were calculated as were Kaplan–Meier estimates of overall survival and relapse‐free survival for some aetiologies. Results Erythroderma represented 0.44‰ of all dermatoses with an age of 55.13 ± 18.16 and no sex predilection. Psoriasis was the predominant aetiology (32.9%) with a median duration of 6.75 years and previous one or more episodes of erythroderma. Psoriasis was significantly associated with pruritus (P = 0.0001), pachyonychia (P = 0.00001), palmoplantar keratoderma (P = 0.0001) and hypereosinophilia (P = 0.008). The latter is then not specific for drug induced erythroderma (P = 0.004). Carbamazepine (27.8%) and penicillin (22.2%) were the most implicated drugs. Positive Clinical–histological correlation was found in 77% of cases (κ = 0.753). Relapse was seen in all aetiologies, but drug reactions and had occurred in the first 3 years in 90% of them. Mortality rate was 11.3 per 1000 patients‐years. Conclusions Our study illustrates the severity of erythroderma. It alters heavily the quality of life of patients which is initially altered by the pre‐existent dermatosis. It may be life threatening as mortality rate is high.     

An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node

Voltage-gated Na(+) channels are composed of pore-forming alpha and auxiliary beta subunits. The majority of Na(+) channels in the heart contain tetrodotoxin (TTX)-insensitive Na(v)1.5 alpha subunits, but TTX-sensitive brain-type Na(+) channel alpha subunits are present and functionally important in the transverse tubules of ventricular myocytes. Sinoatrial (SA) nodal cells were identified in cardiac tissue sections by staining for connexin 43 (which is expressed in atrial tissue but not in SA node), and Na(+) channel localization was analyzed by immunocytochemical staining with subtype-specific antibodies and confocal microscopy. Brain-type TTX-sensitive Na(v)1.1 and Na(v)1.3 alpha subunits and all four beta subunits were present in mouse SA node, but Na(v)1.5 alpha subunits were not. Na(v)1.1 alpha subunits were also present in rat SA node. Isolated mouse hearts were retrogradely perfused in a Langendorff preparation, and electrocardiograms were recorded. Spontaneous heart rate and cycle length were constant, and heart rate variability was small under control conditions. In contrast, in the presence of 100 nM TTX to block TTX-sensitive Na(+) channels specifically, we observed a significant reduction in spontaneous heart rate and markedly greater heart rate variability, similar to sick-sinus syndrome in man. We hypothesize that brain-type Na(+) channels are required because their more positive voltage dependence of inactivation allows them to function at the depolarized membrane potential of SA nodal cells. Our results demonstrate an important contribution of TTX-sensitive brain-type Na(+) channels to SA nodal automaticity in mouse heart and suggest that they may also contribute to SA nodal function and dysfunction in human heart.