Melanom des Analkanals: eine Fallstudie

Zusammenfassung Fragestellung und Hintergrund: Ein anales Melanom ist ein seltenes und aggressives Karzinom. Bei den bisher angewandten unterschiedlichen Operationsverfahren zur Behandlung dieser Erkrankung ergab sich noch keine klare Evidenz dafür, einem Verfahren den Vorzug zu geben. Patienten und Methodik: Ausgewertet wurden die Krankenakten von Patienten mit analem Melanom, die zwischen 1987 und 2004 am H. Lee Moffitt Cancer and Research Institute behandelt worden waren, sowie bereits publizierte Studien zum analen Melanom, die mehr als zehn Patienten mit Ergebnisdaten einschlossen. Ergebnisse: Es wurden zw?lf Patienten gefunden (8% aller Karzinome des Analkanals). Neun waren Frauen mit einem medianen Alter von 67 Jahren (27–86 Jahre). Zum Zeitpunkt der Diagnose wiesen vier Patienten einen Lymphknotenbefall und ein Patient Knochenmetastasen auf. Fünf Patienten erhielten eine abdominoperineale Resektion und sechs eine lokale Exzision. Es wurde eine adjuvante Strahlentherapie mit oder ohne Interferon durchgeführt. Fünf der elf Patienten ohne metastatische Erkrankung hatten ein Rezidiv oder starben w?hrend des 1. Jahres nach Diagnosestellung (vier mit lokaler Exzision und einer mit abdominoperinealer Resektion). Die mediane Zeitspanne bis zum Rezidiv betrug 6,5 Monate (4–31 Monate). Die h?ufigste Lokalisation eines Rezidivs war die Leber. Nur eine Patientin, die mit lokaler Exzision und anschlie?end mit Interferon behandelt worden war, war Langzeitüberlebender (kein Nachweis eines Rezidivs nach 54 Monaten). Schlussfolgerung: Das anorektale Melanom ist eine seltene und sehr schwierige Erkrankung. Das pr?operative Staging beeinflusst den Behandlungszeitplan. Da sich kein nennenswerter überlebensvorteil zeigt, wenn eine abdominoperineale Resektion zur Behandlung der nichtmetastatischen Auspr?gung der Erkrankung eingesetzt wird, sollte eine lokale Exzision als Prim?rbehandlung der Wahl erwogen werden. Die adjuvante Strahlentherapie wird gut vertragen und ist zur Verbesserung der lokalen Tumorkontrolle vielversprechend. übersetzter Nachdruck aus Dis Colon Rectum 2007;50:1004–10; DOI 10.1007/s10350-007-2042-5.     

Bioelectrical impedance, cancer nutritional assessment, and ascites

This report describes our experience in the use of bioelectrical impedance analysis (BIA) as a method of nutritional assessment in a cancer patient with ascites. The BIA was an unreliable measure of body composition in this setting.     

Acute toxicity of Schizolobium parahyba aqueous extract in mice

The herbal extract of Schizolobium parahyba leaves is used commonly in the Brazil central region to treat snakebites. This study evaluates the acute toxicological effects of Schizolobium parahyba aqueous extract in mice 24 h after intraperitoneal administration. Acute toxicity was evaluated using biochemical, hematological and histopathological assays. Alterations in the levels of transaminases, bilirubin, albumin and prothrombrin time were observed, and these are likely to occur due to hepatic injury, which was confirmed by light microscopy. Liver histopathological analysis revealed the presence of lymph plasmocitary inflammatory infiltrate, but no other histopathological alterations were observed in any of the other organs analysed. The data confirm the low toxicity of the extract of Schizolobium parahyba and provide a model for the selection of a dose that does not cause injuries in the organism. Copyright © 2009 John Wiley & Sons, Ltd.     

Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute renal failure

Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute renal failure. BACKGROUND: Interleukin 6 (IL-6) is a pleiotropic cytokine released after endotoxemia, trauma and organ injury. IL-6 may act in cellular proliferation activating transduction signals and Ras/Map cascade or the HGF/c-met axis. We tested the effect of IL-6 in the regeneration of tubular epithelia after acute tubular necrosis (ATN) in rats. METHODS: Rats with glycerol-induced acute renal failure (Gly-ARF) were treated with IL-6 200 microg/kg/day. Functional, histological and immunohistochemical tests were done 24 and 72 h after Gly-ARF to localise mitotic cells (BrdU). The renal expression of c-met (Western-Blot) and circulating levels of HGF (ELISA) were also determined. RESULTS: Rats with Gly-ARF had reduced creatinine clearance that was not influenced by IL-6. The histological appearance of ATN was also unaffected by IL-6. The IL-6 treated rats showed a significant increase in tubular cell proliferation in cortex and medulla, as well as in the expression of c-met protein in the renal cortex, compared to untreated Gly-ARF rats. The plasma HGF concentration was equally elevated in treated and untreated Gly-ARF rats. DISCUSSION: IL-6 stimulates tubular regeneration after Gly-ARF and increases the expression of c-met in the renal cortex. Gly-ARF rats have high circulating levels of HGF that is targeted to act in the injured kidneys by the IL-6 overexpressed renal c-met.     

Effects of melatonin administration to rats with glycerol-induced acute renal failure

Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.     

Enhanced transcription factor DNA binding and gene expression induced by arsenite or arsenate in renal slices

Although the kidney represents a target for the accumulation and toxicity of arsenic, little is known about the molecular targets of arsenic in this organ. Therefore, these studies were designed to examine the molecular impact of arsenite [As(III)] and arsenate [As(V)] at low (nanomolar) concentrations. Precision-cut rabbit renal cortical slices were challenged with As(III) or As(V) for up to 8 h. Neither form of the metal induced overt cytotoxicity as assessed by intracellular K+ levels over this time period at concentrations from 0.01-10 microM. In addition, no alterations in the expression of Hsp 60, 70, or 90 were observed. However, induction of heme oxygenase-1 (Hsp 32) was seen following a 4-h challenge with As(III), but not with As(V). As(III) and As(V) induced DNA binding of AP-1 at 2- and 4-h exposure; following a 6-h exposure there was no difference. Although no alteration in the DNA binding activity of ATF-2 was induced by As(III) or As(V), both forms enhanced the DNA binding activity of Elk-1. Enhanced DNA binding activity of AP-1 and Elk-1 correlated with increased gene expression of c-fos, but not c-jun, at 2 h. c-myc gene expression was also induced by As(III) and As(V), albeit at a later time point (6 h). These results suggest that acute arsenic challenge, by either As(III) or As(V), is associated with discrete alterations in the activity of signaling pathways and gene expression in renal tissue.      

Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG production

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.      

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile diabetes mellitus, diabetes insipidus, optic atrophy and a number of neurological symptoms including deafness, ataxia and peripheral neuropathy. Mitochondrial DNA deletions have been described in a few patients and a locus has been mapped to 4p16 by linkage analysis. Susceptibility to psychiatric illness is reported to be high in affected individuals and increased in heterozygous carriers in Wolfram syndrome families. We screened four candidate genes in a refined critical linkage interval covered by an unfinished genomic sequence of 600 kb. One of these genes, subsequently named wolframin, codes for a predicted transmembrane protein which was expressed in various tissues, including brain and pancreas, and carried loss-of- function mutations in both alleles in Wolfram syndrome patients.