In vitro evaluation of teratogenic effects by time-varying MR gradient fields on fetal human fibroblasts

The purpose of this study was to evaluate the influence on fetal cell growth in vitro of rapidly changing magnetic gradient fields such as those produced by the gradient coils of a typical magnetic resonance (MR) imager. The static magnetic field and the radiofrequency pulses were disabled during all measurements. Human fetal fibroblasts were placed within a specially designed MR-compatible incubation system inside the magnet. Trapezoid-shaped waveforms of 500 and 75 Hz base frequency and an amplitude of 2 mT were applied for 2-24 hours. Proliferation of the cells was monitored for 3 weeks after exposure. Cell cycle analysis was performed until 24 hours after exposure to detect alterations in cell division. Tests were performed under two different conditions of growth to detect increased as well as decreased proliferation effects. None of these tests showed differences in proliferation and cell cycle distribution between exposed and nonexposed cells.     

Lymphocyte subsets in bronchoalveolar lavage after exposure to Actinobacillus pleuropneumoniae in pigs previously immunized orally or by aerosol

Young pigs were immunized with the lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae by aerosol or orally using viable and inactivated bacteria. The cellular changes in the bronchoalveolar lavage (BAL) were studied in repeated lavages after the pigs were infected with live bacteria. The nucleated cells in the BAL were differentiated and lymphocyte subsets determined. There were no major differences between the two routes of immunization or between viable and inactivated bacteria. The immunization induced an increase in all lymphocyte subsets studied and in the appearance of plasma cells and lymphoid blasts. The infection did not cause a further increase except in granulocytes. The lack of a booster-type increase in lymphocytes in the BAL might indicate a different immunologic reaction of the lung or that lymphocytes of the BAL do not represent lung lymphocytes in general. The protective effect of the immunization might be deduced from the increase in lymphocytes after immunization but not from the reaction pattern after infection. Offprint requests to: R. Pabst     

Shunt survival rates by using the adjustable differential pressure valve combined with a gravitational unit (proGAV) in pediatric neurosurgery

Object

Overdrainage is a chronic complication in shunted pediatric patients with hydrocephalus. The use of adjustability of differential pressure (DP) valves in combination with antisiphoning devices may help to overcome this sequela and may diminish the rate of possible shunt failures. The purpose of this retrospective study is to report our experience on shunt survival and infection rate with an adjustable DP valve with integrated gravitational unit in pediatric hydrocephalus.

Methods

The proGAV consists of an adjustable differential pressure (DP) valve and a gravitational unit. During the time period of July 2004 and December 2009, a total of 237 adjustable gravitational valves were used in 203 children (age, 6.5?±?6.54; 0–27 years). In the follow-up period, valve and shunt failures as well as rate of infection were recorded.

Results

Within the average follow-up time of 21.9?±?10.3 months (range, 6–72 months), the valve survival rate was 83.8 %. The overall shunt survival rate including all necessary revisions was 64.3 %. Looking at the group of infants (<1 year of age) within the cohort, the valve survival rate was 77.3 % and the shunt survival rate was 60.9 %. The overall infection rate was 4.6 %.

Conclusion

In a concept of avoiding chronic overdrainage by using the proGAV in hydrocephalic children, we observed a good rate of valve and shunt survival. Compared to previous reported series, we experienced the proGAV as a reliable tool for the treatment of pediatric hydrocephalus.     

Expression of beta-catenin and p53 are prognostic factors in deep aggressive fibromatosis

AIMS: To determine the prognostic significance of beta-catenin in aggressive fibromatosis and to identify potential molecular markers for new targeted therapies. METHODS AND RESULTS: A tissue microarray of 37 cases of deep aggressive fibromatosis was constructed and subjected to immunohistochemical analysis for beta-catenin, p53, smooth muscle actin (SMA), desmin, Ki67, c-erbB2, epidermal growth factor receptor (EGFR), c-kit, CD34 and S100. Complete clinical follow-up was available for 23 patients. Nuclear beta-catenin expression was associated with an increased rate of local tumour recurrence (60.0% 1-year and 0% 5-year event-free survival; P < 0.05). Furthermore, p53 expression was associated with an increased risk of tumour recurrence (50% 1-year event-free survival rate and 0% 5-years event-free survival rate, P < 0.05). The coexpression of p53 and beta-catenin was significantly correlated (P < 0.05). No statistically significant association was seen between MIB1 and p53 or beta-catenin expression, respectively. No expression of EGFR, c-erbB2 or c-kit was seen. CONCLUSIONS: The overexpression of beta-catenin and p53 is associated with a decreased event-free survival in deep aggressive fibromatosis. Further studies are required to establish whether these findings can lead to an improvement in the treatment of this rare neoplasm.     

Autosomal dominant polycystic kidney disease (ADPKD)—mechanisms of cyst formation and renal failure*

None of the hypotheses proposed so far to explain cyst formation in autosomal dominant polycystic kidney disease (ADPKD) is entirely satisfactory, e.g. the theory of tubular obstruction by intraluminal polyps or dilatation of nephron segments as a consequence of abnormal compliance of the basement membrane. Recent in vitro studies show that (i) synthesis of basement membrane material is abnormal and that (ii) the direction of transepithelial resorptive flux into a secretory mode is reversed as a consequence of faulty insertion of Na, K-ATP'ase into the luminal membrane. It remains unclear why cystic transformation of a few percent of nephrons should cause endstage renal failure. Our clinical and experimental studies do not provide evidence to support some hypotheses proposed in the past, i.e. that renal parenchyma is compressed by expanding cysts and that glomeruli are overperfused. Our histological studies show that progression to endstage renal failure is associated with (i) progressive arteriolar lesions (out of proportion to the vascular lesions seen in extrarenal vascular beds; and (ii) progressive interstitial fibrosis. It appears that fibroblasts in ADPKD are particularly sensitive to platelet derived growth factor (PDGF) which is secreted by epithelial cells of the cyst wall in a paracrine fashion. In contrast to previous opinion, which was presumably skewed by ascertainment bias, it appears that not all, and perhaps not even a majority, of ADPKD patients progress to endstage renal failure. Factors related to progression are gender, family history and hypertension. Both abnormal sodium excretion and inappropriate renin secretion play a role in the genesis of hypertension. Elevated blood pressure, albeit within the normotensive range, is demonstrable even in prepubertal children. The involvement of renin in renal vasoconstriction of normotensive ADPKD patients suggests a particular role of ACE inhibitors in the management of these patients.     

Palliation und Frakturprävention

Sind Skelettmetastasen nachweisbar, so ist dies ein untrügliches Zeichen dafür, dass sich die Tumorerkrankung im gesamten Organismus ausgebreitet hat. Eine Heilung ist nur in seltenen F?llen zu erwarten. Die Therapie ist in diesem Stadium eher palliativ. Bei konservativer Therapiestrategie sollte wegen des Risikos von pathologischen Frakturen eine Abstimmung mit dem Chirurgen und Orthop?den erfolgen, um ggf. rechtzeitig operativ zu intervenieren. W?hrend eine pr?ventive operative Stabilisierung im Bereich der langen R?hrenknochen relativ unproblematisch ist, kann sie im Becken- und Wirbels?ulenbereich Komplikationen mit sich bringen.