Renal lesions in von Hippel-Lindau disease: immunohistochemical expression of nephron differentiation molecules, adhesion molecules and apoptosis proteins

AIMS: Renal lesions in von Hippel-Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship. METHODS AND RESULTS: To investigate such a possible relationship between cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel-Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (alpha3, alpha5, alpha6, alphav, beta1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl-2) inconspicuous. CONCLUSIONS: Phenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel-Lindau disease.     

Temporary feed restriction partially protects broilers from necrotic enteritis

The objective of this study was to investigate the effect of feed restriction on the intestinal ecosystem and on the pathogenesis of experimental necrotic enteritis in broiler chicks. To induce subclinical necrotic enteritis, an experimental challenge model using a specific diet formulation, Gumboro vaccination, oral inoculation of broilers with a 10-fold dose of attenuated anticoccidial vaccine and multiple oral inoculations with a specific strain of Clostridium perfringens was adopted. Two hundred and forty 1-day-old Cobb 500 broilers were randomly allocated to four groups: feed restricted, challenged, both feed restricted and challenged, and negative control. At 21, 22, 23 and 24 days of age, the intestines, gizzard and liver were collected from 15 birds in each group and scored for gross lesions. The intestinal digesta was collected for pH and viscosity determination. One caecum from each bird was taken for microbiological analysis. The application of feed restriction in birds challenged with C. perfringens reduced the necrotic enteritis lesion score significantly (P ≤ 0.05) and feed restriction significantly reduced (P ≤ 0.05) pH in the small intestine, the viscosity of the jejunum digesta as well as the C. perfringens counts in the caeca compared with the controls. In conclusion, feed restriction of broilers has a positive effect on the intestinal ecosystem and a significant protective effect against necrotic enteritis in the subclinical experimental model.     

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to 99mTc-DTPA

Respiratory epithelial clearance of 99mTc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113mIn-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.     

Prader-Willi-Labhart syndrome: relations with the hypothalamus and chromosome 15

The Prader-Willi syndrome is a human disease whose physiological causes have not yet been elucidated. However, clinical and biological parameters suggest that it is an hypothalamic disorder. This syndrome is the most common form of human congenital obesity. In many cases, the genetic alteration has been identified as a microdeletion in the chromosomal region 15q11-q13. Consequently, one can presume that obesity in patients with Prader-Willi syndrome is the result of some hypothalamic deficiency involving the products of one or several genes found in this region of chromosome 15. Several DNA markers belonging to this genomic region have been isolated. If these are fragments of expressed genes, it may be possible to examine the possible association of their products with the hypothalamus and the disease. Such studies may provide new insights into the role of the hypothalamus in the pathophysiology of obesity.     

Die Erholung des Myokards nach Herzstillstand durch extrazellulären Natrium- und Kalziumentzug und durch Procaingabe

Zusammenfassung Ein Verfahren zur Verlängerung der tolerierbaren Ischämiezeit des Myokards stellt der vonBretschneider 1964 angegebene Herzstillstand durch Natrium- und Kalziumentzug und Procaingabe dar. Bisher waren der Sauerstoffverbrauch, der anaerobe Stoffwechsel, die Elektrolytbilanzen, sowie die histologisch morphologischen Veränderungen während der Kardioplegie am Hundeherzen untersucht worden. Für die sichere klinische Anwendung mußte die Erholung des Stoffwechsels nach einem solchen induzierten Herzstillstand analysiert werden. Eine erste Versuchsreihe zeigte, daß am isolierten Kaninchenherzen nach 60 min Ischämie bei 18 °C mit dieser Methode zwar eine gerade ausreichende postischämische Erholung des Stoffwechsels möglich ist, daß aber erhebliche Substratverluste mit der Reperfusion auftreten. Die zweite Versuchsreihe am Hundeherzen in situ ergab eine vollständige Erholung des Stoffwechsels innerhalb der ersten 5 min nach einer Ischämie von 60 min bei 25 °C mit der Methode vonBretschneider. Dabei tritt kein Substratverlust mit der Wiederdurchblutung des Koronarsystems auf. Die Summe der Adeninnucleotide bleibt auch während der 60 min Ischämie völlig konstant.Ein Vergleich der Veränderungen der Substrate und Metabolite des Stoffwechsels während der Kardioplegie mit den anderen bisher auch klinisch verwendeten Verfahren ergibt eindeutig die längsten tolerierbaren Ischämiezeiten bei Anwendung dieser Herzstillstandsmethode, so daß die Methode nach dem augenblicklichen Stand der Kenntnisse als das beste Verfahren zur Durchführung eines induzierten Herzstillstandes, d. h. einer notwendigen Myokardischämie gewertet werden muß.

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Summary In 1964Bretschneider introduced a cardioplegia by sodium and calcium depletion and application of procaine which was a new principle for prolongation of the tolerable ischemic period of the myocardium. Untill now the oxygen consumption, the anaerobic metabolism, the electrolyte balances and the histologic changes during this cardioplegia had been investigated in dogs. For a safe clinical use the recovery period after such an induced cardiac arrest had to be evaluated.In a first group of experiments a sufficient postischemie recovery was found after a 60 min period of ischemia at 18 °C with his method of cardiac arrest in isolated rabbit hearts. But a considerable ammount of metabolites was lost during reperfusion with blood.A second group of experiments showed a complete postischemic recovery during the first five minutes after a 60 min period of ischemia at 25 °C introduced by the method ofBretschneider in dogs in situ. There was no loss of metabolites during reperfusion of the coronary system with blood. The sum of adenine nucleotides remained constant throughout a 60 min period of ischemia.The changes of primary substrates and metabolites during this artificial cardiac arrest compared with other clinically introduced methods of cardioplegia showed the longest tolerable ischemic period with the cardiac stand still according toBretschneider. This method must be regarded in the moment as the safest method of induced cardiac arrest for a necessary period of myocardial ischemia.

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Mit 3 Abbildungen und 2 Tabellen     

Stichverletzung von Schädel und Gehirn

Zusammenfassung Es wird über einige Fälle mit Stichverletzung von Schädel und Gehirn berichtet, diagnostische Probleme werden angesprochen. Die Verletzungen werden oft verkannt, weil die äußere Wunde nicht selten harmlos aussieht, keine neurologische Symptomatik vorliegt oder weil klinische Symptome als Folge von Trunkenheit, stumpfem Trauma oder einer Erkrankung interpretiert werden. Die Wichtigkeit einer genauen Untersuchung des Kopfes des Patienten — auch mit der verfeinerten Technik der modernen Radiodiagnostik — wird betont; denn bei richtiger Diagnose in angemessener Zeit ist die Prognose nicht immer schlecht.     

Rectal biopsy and precancer in ulcerative colitis

Forty-seven patients with ulcerative colitis subjected to elective proctocolectomy were investigated with regard to the occurrence of precancerous changes in the rectal biopsy and the operation specimen. In the rectal biopsy from seven patients precancerous lesions were found and in the operation specimens from these patients precancer was also found in other parts of the colon. In five of these patients the precancer was associated with carcinoma and in four of the patients the tumour had not been detected before operation. It is concluded that rectal biopsy is of great value in patients with ulcerative colitis for detection of early cancer and patients at risk of developing a colitis carcinoma.