13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: Report from the childrens cancer study group

The Childrens Cancer Study Group evaluated daily oral 13-cis-retinoic acid to determine its therapeutic efficacy in 28 children with advanced neuroblastoma refractory to conventional therapy. Cheilitis and fissured lips were the most common side effects; however, fewer than 50% of the patients experienced any toxicity. Two of twenty-two evaluable children demonstrated positive response to therapy. In one case, a child received the drug for 11 months. Seventeen patients demonstrated progressive disease within 28 days of the start of treatment. Three other patients with stable disease, or removed from study at day 28, were considered nonresponsive. Our data demonstrate that, when given as a single daily oral dose of 100 mg/m², 13-cis-retinoic acid does not have significant activity in children with advanced neuroblastoma. © 1992 Wiley-Liss, Inc.     

Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 × 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods.     

Acute mastoiditis — Relevant once again

Summary During recent years, a significantly increased incidence of acute mastoiditis was observed at the University Children's Hospital, Tübingen, Germany (1975–1979: 1.4 patients/year; 1987–1992: 4.2 patients/year; p<0.05). We therefore reviewed the records of all patients with acute mastoiditis (n=58) that had been treated at the Children's Hospital between 1975 and 1992 and at the Clinic of Otorhinolaryngology between 1978 and 1992. The male to female ratio was 1.8:1 and 60.4% of the patients were younger than 24 months. Retroauricular swelling was more often observed (n=49) than protrusion of the pinna (n=45) and retroauricular redness (n=38).Streptococcus pneumoniae was the most frequently isolated pathogen. Several factors predisposing for the development of acute mastoiditis were identified. These included withholding antimicrobials for treatment of the preceding episode of otitis media; use of suboptimal agents for therapy of otitis media (penicillin and, possibly, erythromycin ethylsuccinate); and insufficient duration of treatment.

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Akute Mastoiditis — wieder ein aktuelles Problem

Zusammenfassung In den letzten Jahren wurde an der Univ.-Kinderklinik Tübingen eine signifikante Zunahme der Inzidenz der akuten Mastoiditis beobachtet (1975–1979: 1,4 Patienten/Jahr; 1987–1992: 4,2 Patienten/Jahr; p<0,05). Wir analysierten daher die Krankengeschichten aller Patienten mit akuter Mastoiditis (n=58), die zwischen 1975 und 1992 an der Universitäts-Kinderklinik und zwischen 1978 und 1992 an der Universitäts-Hals-Nasen-Ohrenklinik behandelt worden waren. Das Verhältnis von Jungen zu Mädchen betrug 1,8:1, und 60,4% der Patienten waren jünger als 24 Monate. Eine retroaurikuläre Schwellung wurde häufiger beobachtet (n=48) als ein abstehendes Ohr (n=45) und eine retroaurikuläre Rötung (n=38).Streptococcus pneumoniae war der häufigste Erreger. Mehrere für das Auftreten einer akuten Mastoiditis prädisponierende Faktoren wurden gefunden: die Nichtbehandlung der vorausgegangenen Otitis media mit Antibiotika, der Einsatz suboptimaler Antibiotika (Penicillin und möglicherweise Erythromycin-Ethylsuccinat) für die Otitis-Behandlung und eine ungenügende Therapiedauer.

     

Disturbed myelinogenesis and recovery in hyperphenylalaninemia in rats: An immunohistochemical study

Chronic hyperphenylalaninemia (HPA) in rats has been used as an experimental model of the human inborn error of metabolism phenylketonuria (PKU). Impaired brain development in PKU and HPA is reflected in reduced myelin formation. We have used immunohistochemistry, with antibodies to cell-specific antigenic markers, to investigate the cellular basis of the hypomyelination in the corpus callosum and cerebral cortex of rats made hyperphenylalaninemic from Postnatal Days 3-17. The rats were then allowed to recover until Day 59. No effects were seen on the number and differentiation pattern of ganglioside GD3-expressing glial progenitors. Myelin basic protein and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNP) immunostaining demonstrated a reduction in myelin formation in the corpus callosum and subcortical white matter at 12 and 17 days postnatal. However, numbers of CNP+ oligodendrocytes appeared normal throughout development. No reactive astrogliosis was seen at any stage. The intensity of axonal neurofilament immunostaining was reduced in the corpus callosum at 17 days. In layers II and III of the cortical gray matter there was an increase in the cell packing density and a concomitant decrease in cell body size. Myelination in the corpus callosum was rapid during the recovery period with no difference noted at Day 59. Axonal neurofilament staining also returned to normal in the corpus callosum. However, recovery became increasingly incomplete away from the corpus callosum into the cortical gray matter. Our data suggest a primary effect of HPA on axonal maturation with hypomyelination consequential upon this.     

Heroin-Induces Differential Protein Expression by Normal Human Astrocytes (NHA)

Heroin use is postulated to act as a cofactor in the neuropathogenesis of human immunodeficiency virus (HIV-1) infection. Astrocytes, integral components of the CNS, are reported to be susceptible to HIV-1 infection. Upon activation, astrocytes release a number of immunoregulatory products or modulate the expression of a number of proteins that foster the immunopathogenesis of HIV-1 infection. However, the role of heroin on HIV-1 infectivity and the expression of the proteome of normal human astrocytes (NHA) have not been elucidated. We hypothesize that heroin modulates the expression of a number of proteins by NHA that foster the neuoropathogenesis of HIV-1 infection. We utilized LTR amplification and the p24 antigen assay to quantitate the effect of heroin on HIV-1 infectivity while difference gel electrophoresis (DIGE) combined with protein identification through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the effects of heroin on the proteomic profile of NHA. Results demonstrate that heroin potentiates HIV-1 replication in NHA. Furthermore, heroin significantly increased protein expression levels for protein kinase C (PKC), reticulocalbin 1 precursor, reticulocalbin 1, tyrosine 3-monooxgenase/tryptophan 5-monooxgenase activation protein, chloride intracellular channel 1, cathepsin D preproprotein, galectin 1 and myosin light chain alkali. Heroin also significantly decreased protein expression for proliferating cell nuclear antigen, proteasome beta 6 subunit, tropomyosin 3, laminin receptor 1, tubulin alpha 6, vimentin, EF hand domain family member D2, Tumor protein D54 (hD54), ATP synthase, H+ transporting, mitochondrial F1 complex and ribosomal protein S14. Identification of unique, heroin-induced proteins may help to develop novel markers for diagnostic, preventative and therapeutic targeting in heroin using subjects.     

Efficacy of antiperspirants on feet.

Nineteen male soldiers participated in a study of the effectiveness of two antiperspirants (aluminum chlorohydrate and aluminum zirconium tetrachlorohydrex glycine) in reducing foot-sweat accumulation and injuries. Each subject was tested before and after antiperspirant application, with a 1-hour treadmill march at 5.6 km/hour in a warm environment. Both antiperspirants decreased (p less than 0.05) foot-sweat accumulation over 50%. There was also a tendency, although not statistically significant, for subjects to incur fewer blisters with antiperspirant use. However, the antiperspirants also increased (p less than 0.05) the incidence of irritant dermatitis. Nevertheless, these data suggest that the application of antiperspirants to the feet has merit in reducing serious foot injuries (blisters, trench foot) exacerbated by wet feet.     

Airway hypocapnia increases microvascular leakage in the guinea pig trachea.

We have previously shown that airway hypocapnia induced bronchoconstriction in the guinea pig lung by releasing tachykinins. To examine whether airway hypocapnia could also cause an increase in airway microvascular leakage, a tracheal segment was isolated in vivo in anesthetized guinea pigs and unidirectionally ventilated (200 ml/min) for 1 h with fully conditioned air (0% CO2) or isocapnic gas (5% CO2). The lungs were ventilated through a distally placed tracheal cannula. Microvascular leakage was quantitated by the injection of Evans blue (EB) and its extraction from the tracheal segment. EB extravasation was increased in tracheae exposed to 0% CO2 (52.3 +/- 2.0 micrograms/g wet tissue) compared with tracheae exposed to 5% CO2 (26.4 +/- 2.9 micrograms/g; p less than 0.05) and to tracheae from spontaneously breathing guinea pigs (25.2 +/- 2.3 micrograms/g; p less than 0.05). Groups of animals in which trachea were unidirectionally ventilated with 0% CO2 were then pretreated with a range of drugs in an attempt to determine the mediators responsible for the microvascular leakage with 0% CO2. Capsaicin and morphine pretreatment did not significantly alter 0% CO2-induced EB extravasation, and phosphoramidon prevented rather than increased extravasation, suggesting that tachykinins did not play a role. The hypocapnia-induced increase in microvascular leakage was, however, prevented by indomethacin pretreatment and significantly attenuated by dazmegrel, a thromboxane synthetase inhibitor. We conclude that airway hypocapnia causes microvascular leakage in the guinea pig trachea and that this effect is mediated by prostaglandins and/or thromboxane.     

Could bipolar vessel sealers prevent bile leaks after hepatectomy?

BACKGROUND AND AIMS: The aim of this work was to test the feasibility of using a bipolar low thermal acting system inducing collagenic sealing but not protein coagulation to secure hepatic parenchyma cutting. MATERIALS AND METHODS: Thirty consecutive hepatectomies were carried out using kellyclasy plus ligatures and clips (controls), while the following 50 hepatectomies used kellyclasy plus bipolar vessels sealer (BVS). Blood loss, duration of hepatic pedicle clamping, length of hospital stay, and complications were recorded. RESULTS: There was no statistically significant difference in blood loss and duration of clamping between controls and BVS. Specific complications (9/21 in the control group vs 1/49 for the BVS group, p<0.00045) and length of hospital stay (14 days in the control group vs 11 days in the BVS group, p<0.014) were statistically lower in BVS group than in the controls, mainly due to prevention of bile duct leakages. CONCLUSIONS: Our data suggest that BVS may be particularly efficient to achieve bilistasis leading to the highest level of safety in performing hepatectomies. Further studies are now needed to confirm its superiority on the classical biliary ducts occlusion techniques.