Grenzen und Möglichkeiten der Glaskörperchirurgie bei diabetischer Retinopathie

Hintergrund: Verschiedene Indikationen für glask?rperchirurgische Eingriffe bei Komplikationen der diabetischen Retinopathie haben sich etabliert. Jedoch gibt es wenig Daten zu der Frage, in welchen Situationen auf einen Eingriff wegen aussichtsloser funktioneller Prognose verzichtet werden sollte. Material und Methode: Die Krankengeschichten von 389 Patienten, die zwischen 1990 und 1994 in unserer Klinik wegen Komplikationen der diabetischen Retinopathie vitrektomiert worden sind, wurden retrospektiv analysiert. Die Nachbeobachtung betrug mindestens 6 Monate, im Median 26 Monate. Mit multivariaten, logistischen Regressionsanalysen wurden Faktoren ermittelt, die mit schlechten postoperativen, funktionellen Ergebnissen korrelieren. Ein mathematisches Modell wurde entwickelt, welches die Einsch?tzung der Prognose für verschiedene Ausgangssituationen erlaubt. Ergebnisse: Bei 45 Augen (12%) stieg der postoperative Visus nicht über 1/50. Risikofaktoren waren Ablatio der Makula, Ausdehnung der Ablatio, Rubeosis und Dauer der Visusminderung. ?hnliche Risikofaktoren gelten auch für Revisionsoperationen. Bei einem Auge mit totaler Traktionsablatio von über 6 Monaten Dauer und Rubeosis liegt die berechnete Wahrscheinlichkeit für einen postoperativen Visus über 1/50 lediglich bei 2%. Schlu?folgerungen: Bei totaler Traktionsablatio, insbesondere bei Rubeosis und l?ngerem Bestehen der Ablatio, ist die Prognose extrem schlecht. Auf operative Ma?nahmen sollte hier verzichtet werden.      

Respiratory tract infections due to different rhinovirus serotypes and the influence of maternal antibodies on the clinical expression of the disease in infants.

Rhinoviruses were isolated from nasopharyngeal secretions of 49 children hospitalized because of severe respiratory tract infection. The isolates were typed using 90 type-specific antisera. No obvious relation between certain serotypes and the severity of illness was found. Serum samples were drawn from all children simultaneously with the nasopharyngeal secretions and screened for the presence of type-specific neutralizing antibodies. Children aged 1 week to 6 months had higher neutralizing antibody titers and revealed a lower degree of morbidity than older children. The decline of neutralizing serum antibodies with increasing age was correlated with a higher incidence of severe disease in those aged 7-12 months. Nevertheless, also in this age group children with mild clinical courses of disease were observed despite a low concentration or an absence of neutralizing serum antibodies. This indicates that not only neutralizing serum antibodies, but other factors also influence the clinical expression of RHV-induced disease.     

Combined high-efficiency hemodialysis and charcoal hemoperfusion in severe N-acetylprocainamide intoxication.

Several extracorporeal techniques have been used to remove N-acetylprocainamide (NAPA), the major metabolite of procainamide, in patients intoxicated with this substance. We report a patient with life-threatening NAPA intoxication who was rapidly and successfully treated with combined high-efficiency hemodialysis and charcoal hemoperfusion. The hemodialyzer and hemoperfusion cartridge were placed in series such that the patient's blood was dialyzed before reaching the cartridge. Overall clearance of NAPA was 153 mL/min, with clearance due to hemodialysis averaging 102 mL/min and that due to hemoperfusion averaging 88 mL/min. Thus, addition of the hemoperfusion cartridge into the extracorporeal circuit resulted in a 50% increase in clearance over that obtainable by high-efficiency hemodialysis alone. In comparison to other modalities, this technique is more effective than either hemodialysis or charcoal hemoperfusion alone and can achieve a more rapid reduction of serum NAPA levels than that observed with slow continuous hemofiltration or hemodiafiltration.     

Tender points, depressive and functional symptoms: Comparison between fibromyalgia and major depression

Summary The degree of symptomatic overlap between fibromyalgia and major depression should be estimated by assessing the amount of local tenderness and the frequency and severity of depressive and functional symptoms. Tender points were assessed by palpation and symptoms by psychometric scales in 30 patients with fibromyalgia and 26 patients with major depression. The patients with fibromyalgia had markedly more tender points (16.5) than the depressive patients (1.3). In contrast, depressive and functional symptoms were present in both groups of patients, and some depressive patients (26%) also suffered from clinical pain. An increased sensitivity to pressure pain clearly distinguishes fibromyalgia from depression even if there is an overlap of other symptoms.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Up-regulation of cathepsin X in Helicobacter pylori gastritis and gastric cancer

Recently, we identified increased cathepsin X expression in H. pylori-infected gastric mucosa. Here, we describe further up-regulation in gastric cancer and report on the role of inflammatory cytokines required for cathepsin X up-regulation in H. pylori-infected gastric mucosa, as well as on consequences for cellular invasion. Biopsy specimens were taken from the antrum, corpus and cardia of H. pylori-infected and non-infected patients. Gastric cancer samples were obtained from patients undergoing gastric surgery. Cathepsin X was detected in gastric mucosa by quantitative real-time RT-PCR, western blotting and immunohistochemistry. Induction of cathepsin X expression in epithelial and inflammatory cells caused by H. pylori infection was tested in in vitro contact and non-contact co-cultures of AGS cells and monocytic cells. Patients with H. pylori gastritis showed significantly higher cathepsin X mRNA (2.5-fold) and protein (1.6-fold) expression than H. pylori-negative patients. Cathepsin X was also up-regulated in gastric cancer (3-12-fold) compared to non-neoplastic mucosa. Cathepsin X was predominantly expressed by macrophages in the mucosal stroma and in glands of the antral mucosa. In addition, tumour cells stained for cathepsin X in 26 (68%) patients with gastric carcinoma. In general, staining was significantly more common (20 vs. 6 patients) and more intense (3.55 vs. 0.83) in intestinal type gastric cancer than in the diffuse type. In vitro cell culture experiments revealed that intercellular signalling between pathogenicity island (PAI)-positive H. pylori-infected epithelial cells and macrophages via soluble factors in the culture medium seems to be responsible for increased expression of cathepsin X in monocytes. Using antisense oligonucleotides, cathepsin X up-regulation was directly associated with higher invasiveness in vitro. Although no correlation of cathepsin X expression and TNM stage was found, our study demonstrates that cathepsin X plays a role not only in the chronic inflammation of gastric mucosa but also in the tumourigenesis of gastric cancer.     

Renale und enterale Elimination der Koproporphyrin-Isomeren bei Rotor-Syndrom

Summary Urinary and fecal total, isomer I, and isomer III coproporphyrin excretion of a Rotor's syndrome patient and his family were determined. The proprositus showed increased urinary total coproporphyrin excretion (248 µg/24 h) and a shift of the coproporphyrin isomer I/III relation (70%/30%). The propositus's father and two siblings also had elevated renal excretion of coproporphyrin I. Total coproporphyrin excretion was enhanced only in the propositus's father and one sibling, while being normal in another sibling. All family members that could be investigated showed considerably decreased fecal porphyrin excretion. In Rotor's syndrome porphyrin excretion is mainly renal. The coproporphyrin isomer I/III relation is shifted towards isomer I. Phenotypically normal relatives with normal bilirubin plasma levels may have alterations in both their renal and enteral coproporphyrin excretion.

Herrn Professor Dr. med. N. Zöllner zum 65. Geburtstag gewidmet