N-PEP-12 – a novel peptide compound that protects cortical neurons in culture against different age and disease associated lesions

Summary. The neuroprotective potency of N-PEP-12, a novel, proprietary compound consisting of biopeptides and amino acids was investigated. Lesion models have been applied in neuronal cultures of embryonic chicken cortex, pre-treated with N-PEP-12 from the first day onwards. On day 8 in vitro neurons were lesioned and cell viability was measured 24 and 48 hours later. To simulate acute brain ischemia, cytotoxic hypoxia was induced by sodium cyanide or by iodoacetate and excitotoxicity by L-glutamate. Ionomycin for up to 48 hours induced calcium overload. The cytoskeleton was disrupted by addition of colchicine. N-PEP-12 shows dose-dependent neuroprotection in all different models. The effect size depends on the recovery time but also on the extent of the lesion. In cases of mild to moderate lesion pronounced dose-dependent effects could be demonstrated. This indicates that chronic exposure to N-PEP-12 is able to prevent neuronal cell death associated to conditions occurring during normal aging and neurological disorders like ischemic stroke, hypoxia, brain trauma, or AD.     

The advantages of axillary artery cannulation in surgical treatment of type A acute aortic dissection

There are more alternative cannulation techniques during surgery of type A aortic dissection. The most frequently used femoro-atrial cannulation method provides limited possibility for brain protection during surgery. This theory is confirmed by relatively high frequency of major brain complications in patients operated on while using this cannulation technique. During the last years cannulationis used more often, as it may provide more protection for the brain than other methods. In 2003 seven patients underwent aortic reconstruction because of type A acute aortic dissection using axillary cannulation. All patients except one were discharged after uneventful recovery. There were no postoperative neurological complications following surgery. We lost one patient due to distal progression of the dissection. He was the only patient with clinical evidence of transient postoperative brain damage. We are strongly convinced that the spectacular improvement in our results for the surgery of type A acute aortic dissection is due to the axillary cannulation, the anterograde flow and the isolated cerebral perfusion. We recommend the axillary cannulation technique as the first choice in type A acute aortic dissection.     

Rapid, painless unilateral vision loss in a 37-year-old healthy woman

A 37-year-old woman experienced painless, progressive vision loss to no light perception in the left eye over the course of 3 days. The right eye was unaffected. On examination, the only other abnormal finding was a +4 left afferent pupillary defect. She was initially diagnosed with retrobulbar optic neuritis and admitted for treatment with intravenous methylprednisolone. Neuro-imaging revealed a large right anterior cerebral artery aneurysm that crossed the midline to compress the left optic nerve. The aneurysm was treated with coil embolization, which was technically successful but which did not lead to significant improvement in vision.     

Treatment of periodontitis associated with cyclosporin-induced severe gingival hyperplasia with regular mechanical plaque removal in a patient with renal transplantation (Case report)

A clinical case of a middle-aged kidney transplanted woman is presented. The woman has been taking Cyclosporin-A for over 13 years and has had advanced periodontitis and severe gingival swellings and gingival inflammation. The kidney transplant patient was treated and followed up for approx. four years. The treatment protocol included very thorough mechanical scaling and root planing, oral hygienic instructions and the regular professional maintenance program resulted in complete remission of the gingival overgrowth and stabilization of the periodontal condition. The gingival and periodontal conditions showed a continuing improvement over the time despite of the continuous CSA administration.     

Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons

Summary. Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides (<10 k DA) and a mixture of approximately 75% free amino acids, this being based on the total nitrogen content. In this study we used a low serum (2% serum supplement) cell stress in-vitro model to assess drug effectiveness on neuronal viability and programmed cell death (PCD). In this in-vitro model the type of cell death was previously shown to be primarly apoptotic, which was verified by DNA-laddering and TUNEL-staining. For evaluation of neuronal viability a MTT-reduction assay was performed after 4 DIV and 8 DIV and the percentage of apoptotic neurons was determined by bis-benzimide staining of nuclear chromatin. To differentiate between possible effects of the free amino acids and the peptide fraction of Cerebrolysin an artificial amino acid mixture (AA-mix) was used as a control. Cerebrolysin, the AA-mix and 10% foetal calf serum (FCS) caused a similar increase in viability after 4 DIV, whereas the effects of the growth factors BDNF and FGF-2 were less pronounced. After 8 DIV Cerebrolysin, but not the AA-mix, was able to ameliorate neuronal viability, which could reflect a neuro-protective effect or an increased activity of the mitochondrial dehydrogenase measured in a MTT-reduction assay. The percentage of cells showing apoptotic chromatin changes was significantly reduced (p < 0.01) in cultures treated with Cerebrolysin, whereas the AA-mix failed to decrease the percentage of cells showing apoptotic chromatin changes. These findings ascertain an anti-apoptotic effect of the peptide fraction of Cerebrolysin and reveal a transient viability promoting effect of the amino acid fraction, which is most likely due to improved nutritional supply. Received June 7, 2000; accepted November 2, 2000     

A randomized-controlled clinical trial evaluating clinical and radiological outcomes after 3 and 5 years of dental implants placed in bone regenerated by means of GBR techniques with or without the addition of BMP-2

Objective: The aim of this randomized-controlled clinical trial was to evaluate the long-term outcome of implants placed in bone augmented with a xenogenic bone substitute material and a collagen membrane with or without the addition of recombinant human bone morphogenetic protein-2 (rhBMP-2).
Material and methods: Eleven patients received a total of 34 implants placed into sites exhibiting lateral bone defects. In a split mouth design, the defects were randomly treated with the graft material and the collagen membrane either with (test) or without (control) rhBMP-2. The patients were examined 3 and 5 years after insertion of the prosthetic restoration. Student's paired t -test was performed to detect differences between the two groups.
Results: The survival rate at 3 and 5 years was 100% for both groups. The peri-implant soft tissues were stable and healthy without any difference between the two groups. The prosthetic reevaluation demonstrated four loose prosthetic screws during the first 3 years and seven ceramic chippings after 3 and 5 years. The mean distance between the first bone to implant contact to implant abutment junction at 3 years was 1.37 mm (test), 1.22 mm (control), and 1.38 mm (test), and 1.23 mm (control) at 5 years. The difference of <0.2 mm between test and control implants was not statistically significant. The mean change of the marginal bone level between baseline and 5 years ranged from −0.07 mm (mesial, test), −0.11 mm (distal, test), −0.03 mm (mesial, control), to +0.13 mm (distal, control). No statistically significant differences were observed between test and control sites.
Conclusion: Implants placed in bone augmented with and without rhBMP-2 revealed excellent clinical and radiological outcomes after 3 and 5 years.     

Außerklinische Beatmung

Home mechanical ventilation (HMV) is a well-established treatment option for chronic ventilatory failure. The following conditions must be fulfilled for HMV to be indicated: 1) symptoms of chronic ventilatory failure such as dyspnea, morning headache, edema, or symptoms of sleep-disordered breathing, 2) evidence of an underlying disorder that may result in chronic ventilatory failure, such as chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome, restrictive thoracic disorders, or neuromuscular disorders, and 3) evidence of chronic ventilatory failure with specific criteria for different groups of patients. HMV is suggested to improve several outcome parameters, including blood gases, sleep quality, physical capacity, and pulmonary hemodynamics. More important, HMV substantially improves survival, particularly in patients with restrictive diseases. However, in COPD patients, this is still debated. Quality of life has also been shown to improve following commencement of HMV; studies using modern assessment tools have established substantial and enduring quality-of-life benefits in all disease categories.     

Transcutaneous PCO2 monitoring during initiation of noninvasive ventilation

BACKGROUND: To assess the efficacy of transcutaneous Pco2 (Ptcco2) measurements for monitoring alveolar ventilation in patients requiring noninvasive positive-pressure ventilation (NPPV). METHODS: In a prospective study on method agreement pairs of Paco2 and Ptcco2 (SenTec Digital Monitor; SenTec AG; Therwil, Switzerland), measurements were performed every 10 min during the establishment of NPPV over a 4-h period in 10 patients (8 patients with COPD) presenting with acute-on-chronic hypercapnic respiratory failure, thus providing 250 pairs of measurement. RESULTS: Mean (+/- SD) Paco2 decreased from 67.2 +/- 11.9 mm Hg (Ptcco2, 65.5 +/- 13.9 mm Hg) to 54.6 +/- 8.8 mm Hg (Ptcco2, 47.8 +/- 8.8 mm Hg), and mean pH increased from 7.36 +/- 0.03 to 7.44 +/- 0.04. Following Ptcco2 assessment, Ptcco2 in the ensuing 2-min period was the strongest predictor for Paco2 compared to Ptcco2 in the ensuing 5-min period and to real-time measurements. Ptcco2 was highly correlated with Paco2 (r = 0.916; p < 0.001), as determined by linear regression analysis. The mean difference between Paco2 and Ptcco2 was 4.6 mm Hg, and the limits of agreement (bias +/- 1.96 SDs) ranged from -3.9 to 13.2 mm Hg, following the Bland and Altman analysis. Retrospective drift correction produced an even higher correlation (r = 0.956; p < 0.001) with lower limits of agreement (-1.7 to 7.5 mm Hg). CONCLUSIONS: Ptcco2 measurements provide a sensitive, continuous, and noninvasive method for monitoring alveolar ventilation in patients who are receiving short-term NPPV therapy. Drift correction of Ptcco2 measurements improves the accuracy of Ptcco2 monitoring compared to the "gold standard" Paco2 assessment. A lag time of approximately 2 min is present for reliable Ptcco2 values compared to Paco2 values. However, individual variance between Paco2 and Ptcco2 cannot be excluded. Trial registration: www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html Identifier:UKF001271.     

Impairment of respiratory muscle function in pulmonary hypertension

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.5; 25 patients with pulmonary arterial hypertension and six patients with chronic thromboembolic PH) and in 31 control subjects (20 females and 11 males) well-matched for gender, age and BMI (body mass index). A 6-min walking test was performed to determine exercise capacity. Volitionally assessed maximal inspiratory (7.5+/-2.1 compared with 6.2+/-2.8 kPa; P=0.04) and expiratory (13.3+/-4.2 compared with 9.9+/-3.4 kPa; P<0.001) mouth pressures, sniff nasal (8.3+/-1.9 compared with 6.6+/-2.2 kPa; P=0.002) and transdiaphragmatic (11.3+/-2.5 compared with 8.7+/-2.5 kPa; P<0.001) pressures, non-volitionally assessed twitch mouth (1.46+/-0.43 compared with 0.97+/-0.41 kPa; P<0.001) and transdiaphragmatic (2.08+/-0.55 compared with 1.47+/-0.72 kPa; P=0.001) pressures during bilateral anterior magnetic phrenic nerve stimulation were markedly lower in patients with PH compared with control subjects. Maximal inspiratory mouth (r=0.58, P<0.001) and sniff transdiaphragmatic (r=0.43, P=0.02) pressures were correlated with the 6-min walking distance in patients with PH. In conclusion, the present study provides strong evidence that respiratory muscle strength is reduced in patients with PH compared with well-matched control subjects. Furthermore, the 6-min walking distance is significantly linked to parameters assessing inspiratory muscle strength.