The use of a self-expandable aortic stent to incarcerate microcoils and to create a favourable infrarenal neck in an unusual case of endovascular abdominal aortic aneurysm repair.

INTRODUCTION: We report a case of an emergency high-risk patient with a pararenal aortic aneurysm. REPORT: Our patient had a pararenal aneurysm with two components: a wide-neck saccular aneurysm below the left renal artery and a fusiform aneurysm. A self-expandable aortic stent was deployed covering both renal arteries, the saccular aneurysm was embolised with microcoils and a bifurcated aortic endograft was anchored inside the aortic stent. The aortic stent imprisoned the microcoils and avoided proximal type I endoleak. The tomography done 15 months after the procedure showed no endoleaks. DISCUSSION: A self-expandable aortic stent can provide an alternative for emergency high-risk patients with pararenal aortic aneurysms.

Profiling type I collagen gene expression in growing mandibular structures.

We conducted a temporal gene expression analysis with type I collagen in the coronoid process, alveolar process and mandibular angle of the rat. We observed gene expression cross-sectionally across different important physiological time points in the rat postnatal life in order to observe in which developmental stage mandibular development mainly occur. This study indicates prominent type I collagen expression at day 10 postpartum in the mandibular ramus and at day 21 in the alveolar process. These findings correspond well with previously obtained data from proliferation studies in facial bone suggesting that craniofacial growth in the rat occurs mainly between days 10 and 21.

Different bone sesitivity to malformations induced by procarbazine in fetal rats.

The study aimed at to induce cleft-lip-alveolus-palate (CLAP) applying procarbazine in rat fetuses at the 14(th) day of pregnancy, to supply thiocyanate and/or folic acid sufficient for preventive treatment and subsequently to investigate cleft extent in the palatal area as well as bone maturity. In this animal model, female primiparous inbred rats (LEW.1A) were used. The gravid animals were separated into treatment groups: group K (control), group P (procarbazine), group TP (thiocyanate and procarbazine) and group FTP (folic acid, thiocyanate, procarbazine). The results reveal that procarbazine may induce clefts in the palate area. Clefts occurred most frequently in group TP and mainly comprised subtotal clefts of the posterior secondary palate. As for palatal length, group FTP displayed the longest palate which was significantly different only from group K. A different picture was shown for the secondary palate with group TP displaying the shortest values which were significantly different from those in groups K, P, and FTP. Thus, group TP showed the most marked negative changes both for cleft frequency and palatal length as compared to group K and the other groups. The preventive application of either thiocyanate (TP) or thiocaynate and folic acid combined (group FTP) failed to completely prevent cleft formation in the palate area. In conclusion, a preventive effect on palatal clefts and growth inhibition could not be proved for the vitaminoid thiocyanate.

Development of an improved protocol to analyse gene expression in temporomandibular joint condylar cartilage of rats using DNA microarrays.

PURPOSE: During recent years, gene expression analyses based on DNA chip technologies have allowed for the genome-wide identification of genes potentially associated with growth processes in a variety of organs. The present study aims to identify genes differentially expressed in the growing temporomandibular joint cartilage by means of transcriptome analyses. MATERIAL AND METHODS: In total, the condylar cartilage of 32 rats comprising 4 age groups (newborn, 10 days, 21 days, 8 weeks) were used for analysis. Transcriptome analyses were carried out using Affymetrix Expression Arrays (Rat Genome 230 2.0 Arrays). The availability of high-quality RNA preparations from homogeneous tissue samples is a fundamental precondition of successful transcriptome analyses using DNA arrays. An optimised preparation protocol allowed RNA isolation of sufficient quality which was validated using capillary electrophoresis. RNA collected from 8 test animals of the 4 age groups respectively was mixed in equimolar RNA pools which served for the transcriptome analyses using Affymetrix arrays. RESULTS: Statistical analysis of the gene expression data indicated the existence of genes differentially regulated in the growing temporomandibular cartilage. This evidence, however, requires validation by RT-PCR using individual animals' RNA. Preliminary candidate genes belong, among others, to the groups of matrix-degrading proteases, protease inhibitors and genes involved in cell growth, apoptosis and bone remodelling. CONCLUSION: These differentially expressed genes in TMJ growth identified using DNA array technology may possibly contribute to a better understanding of growth biology and provide an approach to necessary therapy.

Cardiac surgery for octogenarians--a suitable procedure? Twelve-year operative and post-hospital mortality in 641 patients over 80 years of age.

OBJECTIVES: The increase in life expectancy as a result of therapeutic improvements subsequently leads to a large number of patients with advanced age. The aim of this study was to review the 30-day mortality and mid-term outcome of octogenarians undergoing coronary artery bypass grafting (CABG) or valve replacement (AVR/MVR). METHODS: The data of 641 patients with a mean age of 82.6 years (range 80.0 - 92.6), operated between 9/93 and 12/05, were reviewed. 432 patients underwent CABG, 188 had AVR and 21 had MVR. We analysed peri-/postoperative mortality and clinical outcomes. Follow-up was obtained by phone contact with patients or their physician. Mid-term survival was determined for the whole population by the Kaplan-Meier method; peri- and postoperative risk factor analysis was done using logistic regression. Follow-up ranged from 0.1 to 11.8 years (mean 3.6 +/- 2.6) and was complete for 99%. RESULTS: We observed a perioperative mortality of 8.8% for CABG, 4.8% for AVR and 9.5% for MVR. Perioperative mortality was strongly associated with urgent/emergent operations (P < 0.03), poorer clinical status (P < 0.03), renal dysfunction (P < 0.05) and male gender (P < 0.04). Actuarial survival after 3, 5 and 8 years was as follows: CABG 78%, 66% and 44%; AVR 79%, 68% and 38%; MVR 76%, 61% and 23%. The mean NYHA functional class for survivors improved in the group of patients with CABG from 2.7 to 2.0 (P < 0.03), in the AVR group from 2.8 to 2.0 (P < 0.03), and in the MVR group from 2.9 to 2.3 (P < 0.05). More than 80% of all surviving patients live at home, either alone or with their family. CONCLUSION: In our cohort of octogenarians, cardiac surgery was found to be associated with an acceptable, although increased perioperative mortality. Despite the enhanced perioperative risk, the clinical benefit, as verified by improved functional status and satisfactory mid-term survival rates, justifies surgery in these patients with advanced age.

Do folic acid and thiocyanate have a preventive effect on exogenously induced disturbances of embryonic cranial development?

The preventive influence of folic acid and thiocyanate on procarbazine-induced disturbances of embryonic cranial development was investigated on experimental animals. Low dosages of folic acid or thiocyanate demonstrated no prophylactic effect. When thiocyanate was administered alone, an increased cleft rate was unexpectedly found for the secondary palate. The combined application of folic acid and thiocyanate showed a cleft-prophylactic effect in the secondary palate in addition to growth protection in the primary palate. It can be assumed that thiocyanate has a positive effect on chondral and osseous growth of the palate during the post-sensitive phase of embryogenesis, while in the sensitive phase, it can function as a carrier for teratogenous and toxic substances.

The influence of procarbazine and thiocyanate on embryonic bone maturation

The substance procarbazine (Natulan®) is a teratogen known to induce cleft palates in rats on day 14 post-conception. The application of thiocyanate (SCN-) alone to rats on day 10 and 14 of pregnancy had no effects on fetal bone maturation. However, when procarbazine was used, the maturation and growth of fetal bones was delayed. Upon additional application of thiocyanate, the effects of procarbazine (Natulan) were increased. Thus, no antiteratogenic effect of thiocyanate occurs. We propose that charge and metabolites of teratogenic agents play a key role in developing the effects of thiocyanate (AU)

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[Simultaneous carotid endarterectomy and cardiac surgery-additional risk factor or safe procedure?]. / Thrombendarteriektomie der Arteria carotis und simultane Herzoperation. Zusätzlicher Risikofaktor oder sichere Vorgehensweise?

BACKGROUND: The occurrence of severe carotid artery disease in more than 12% of patients requiring ACB results in a discrepancy concerning the best treatment for both diseases. We reviewed the early outcome of patients with ACB and/or valve replacement and simultaneous carotid endarterectomy (TEA). METHODS: We evaluated retrospectively 244 patients operated simultaneously between 7/94 and 10/2001: 209 patients received ACB, 35 patients ACB and/or valve replacement. Mean age was 68 years. 188 patients were male. We analyzed risk factors, morbidity, incidence of neurological complications and 30 day mortality. RESULTS: Perioperative stroke with hemiplegia occurred in 3.3% (8 patients). Of these patients, 4 showed contralateral carotid artery occlusion, 2 contralateral severe stenosis. Two patients (0.8%) experienced prolonged reversible ischemic neurological deficit (PRIND), 4 patients (1.6%) transient ischemic attack (TIA). 30-day morbidity was 4.5%. Three patients died due to low cardiac output, 6 patients due to extracardial reasons, 2 patients (0.8) due to cerebral death. CONCLUSION: Simultaneous TEA and cardiac surgery can be performed with an acceptable risk for neurological complications and mortality. Occlusion of the contralateral carotid artery could be identified as an evident predictor for increased neurological complications. Compared to two-stage procedures, combined operations yield a reduction of hospital costs.

Simultaneous carotid endarterectomy and cardiac surgery--additional risk factor or safety procedure?

BACKGROUND: The occurrence of severe carotid artery disease in more than 12 % of patients requiring CABG results in a discrepancy concerning the best treatment for both diseases. We reviewed the early outcome of patients with CABG and/or valve replacement and simultaneous carotid endarterectomy (CEA). METHODS: We evaluated retrospectively 244 patients operated simultaneously between 7/94 and 10/2001. 209 patients received CABG; 35 patients CABG and/or valve replacement. Mean age was 68 years. 188 patients were male. We analyzed risk factors, morbidity, incidence of neurological complications and 30 day mortality. RESULTS: Perioperative stroke with hemiplegia occurred in 3.3 % (8 patients). 4 of these patients showed contralateral carotid artery occlusion, 2 contralateral severe stenosis. 2 patients (0.8 %) experienced prolonged reversible ischemic neurological deficit (PRIND), 4 patients (1.6 %) transient ischemic attack (TIA). 30-day lethality was 4.5 %. 3 patients died due to low cardiac output, 6 patients due to extracardial reasons, 2 patients (0.8 %) developed a cerebral death. CONCLUSIONS: Simultaneous CEA and cardiac surgery can be performed with an acceptable risk for neurological complications and mortality. Occlusion of contralateral carotid artery could be identified as an evident predictor for increased neurological complications. Compared to two-stage procedures, combined operations yield a reduction of hospital costs.

Is it possible to prevent cleft palate by prenatal administration of folic acid? An experimental study.

OBJECTIVE: In this study, folic acid was tested for its antiteratogenic effects on experimentally induced cleft palate in animals. DESIGN: Eleven pregnant Lew 1 A dams (75 fetuses) received 200 mg/kg procarbazine via gastric tubing on postconception (p.c.) day 14 to induce a cleft palate (CP); seven of the pregnant dams (45 fetuses) were additionally given 4 mg/kg folic acid subcutaneously from the 14th to the 17th day p.c. As a control group, three more pregnant dams (24 fetuses) were not treated with the drugs mentioned above. All fetuses were delivered by Caesarian section on day 20 p.c. OUTCOMES MEASURED: All fetuses were weighed and examined macroscopically with a stereomicroscope. Each fetal head was cut into 35 frontal sections and scrutinized histologically. RESULTS: None of the control fetuses (n = 24) exhibited a cleft. Without folate administration, 90% of the fetuses (27 of 30) that received procarbazine exhibited a CP. After additional prenatal folate administration, this rate remained virtually unchanged (91%; 41 of 45). However, the proportion of complete (total) CP (4%) was significantly (p <.0001) lower than in the group without folate (53%). Cleft-associated microgenia and microglossia were also significantly less frequent when folate was administered prenatally: microgenia was reduced by 22% (p =.029) and microglossia by 24% (p =.032). CONCLUSIONS: On the basis of these results, folate has a partial ameliorating effect on the teratogenicity of procarbazine given to pregnant rats. Additional studies are necessary on the effect of folate in different species, also taking cleft lip and CP into consideration.

Intraoperative local fibrinolysis as emergency therapy after early coronary artery bypass thrombosis.

OBJECTIVE: Acute graft occlusion early postoperatively after coronary artery bypass grafting (CABG) is a rare but dramatic complication, frequently making resuscitation necessary. Emergency reoperation with reanastomosing of the concerning grafts is the normal procedure to restrict the otherwise unavoidable myocardial damage. Mortality in these cases is up to 50%. Due to this unsatisfying situation, we perform since 1995 in such cases an adjuvant intraoperative intracoronary installed fibrinolysis with recombinant tissue type plasminogen activator (rt-PA; alteplase). METHODS: Between 1/1994 and 8/1998, 4231 patients underwent CABG. In 18 of these patients, emergency reoperation within the first 12 h after CABG due to clinical signs of acute myocardial infarction was necessary. In nine of the patients (group II) additionally intraoperative rt-PA lysis of the involved vessel/s has been performed. When the peripheral anastomosis was reopened and the thrombotic material was removed, we inserted for this a left atrial-catheter (LA-catheter) of 1.2 mm in diameter, into the coronary artery. Then we administered within 3-5 min, up to 100 mg rt-PA (t1/2: 5-9 min.) locally into the vessel. All patients were treated postoperatively with acetylsalicyl acid (ASA) and heparine. RESULTS: In group I (n = 9; seven males, two females) without thrombolytic therapy, 78% of the patients (n = 7) could not have been prevented from large myocardial infarction despite emergency reoperation. Three of these patients died during or early after reintervention. In group II with fibrinolytic therapy (n = 9) three of the patients developed Q-wave myocardial infarction following reoperation. None of the patients died. Creatinkinase maximum were in group I significantly higher than in group II (group I: CK = 1254 units/I, CK-MB = 197 units/l; group II: CK = 502 units/l, CK-MB = 61 units/l; P < 0.01). Postoperative bleeding was considerable elevated in both groups. In group I, 832 ml/24 h (375-1420 ml), in group II 1164 ml/24 h (520-1560 ml). Lysis-associated complications were not observed. CONCLUSIONS: Reoperation of patients with acute thrombotic bypass occlusion after CABG is characterized by a high mortality and morbidity. If additionally fibrinolysis is performed, a sufficient myocardial perfusion seems to be restored. A short half-life in combination with the presented non-systemic application technique of rt-PA seem to prevent unpredictable bleeding. Rt-PA lysis apparently contributes very effectively to the restoration of the macro- and microcirculation within the infarct-related area. Thrombolytic therapy during cardiac surgery with rt-PA is feasible, its application easy and harmful complications are not seen.

Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer's disease parietal cortex.

Nerve growth factor (NGF) mRNA and protein levels were determined in parietal cortex samples from both normal and Alzheimer's disease (AD) patients. NGF protein levels were slightly elevated in AD patients compared to controls, but NGF mRNA levels were unchanged in the same tissue samples. Thus, small but reproducible increases in NGF protein reported in AD cortex do not result from increases in NGF mRNA.

Levels of NGF protein do not correlate with changes in innervation of the rat iris in old age.

We have examined the hypothesis that alterations in target levels of NGF protein lead to selective changes in peripheral nerve fibres in maturity and old age. NGF levels were assayed using 2-site ELISA in the iris of young and old rats. NGF levels in the iris showed no significant change in old age and did not correlate with age-related changes in the density of NGF-sensitive irideal sympathetic and sensory nerve fibres. Following sympathectomy, NGF levels increased substantially in old but not in young irises, possibly because the lower density of aged sensory nerves resulted in reduced capacity for NGF uptake. Content and uptake of NGF in sympathetic (SCG) neurones was shown to be reduced in old age, while NGF content of the sensory (trigeminal) ganglion increased in old age. Thus NGF levels in neurones, as well as targets, fail to correlate with peripheral nerve fibre growth or atrophy.

Enhanced sympathetic neurite outgrowth on rat hippocampal tissue sections following septal lesions.

Cryostat sections of the rat hippocampus were used as tissue culture substrates for embryonic chick sympathetic explants. Neurite outgrowth from these explants was found to be significantly greater on sections taken from animals with septal lesions as compared to those receiving sham operations. This finding suggests that septal denervation leads to hippocampal substrate changes that enhance sympathetic neurite outgrowth in vitro, perhaps analogous to the sympathetic sprouting response that occurs in vivo.

Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis.

The current study analyzed NGF protein levels in the brains of patients with Alzheimer's disease (AD) as compared with aged neurologically normal individuals. An established two-site ELISA was used to measure NGF-like immunoreactivity in the hippocampus, superior temporal gyrus, superior frontal gyrus, inferior parietal lobule, frontal and occipital cortical poles, cerebellum, amygdala, putamen, and nucleus basalis of Meynert (nbM). ChAT activity was assayed in adjacent tissue samples. NGF levels were also evaluated in Parkinson's disease for comparison with both AD and age-matched control cases. Regardless of the brain bank (University of Cincinnati, Rush Presbyterian St. Luke's Medical Center in Chicago, or University of Alabama at Birmingham), NGF-like activity was at least moderately increased with AD in virtually every brain region examined except for the nbM, in which significant declines were observed. NGF levels were also increased when compared with age-matched Parkinson's cases (frontal cortex). NGF-like activity was not related to age at onset or disease duration in AD cases, nor did NGF levels correlate with age at death in the control or AD groups. Correlations between ChAT and NGF-like activity across brains varied considerably and were generally not significant. The present findings indicate that AD is characterized by a widespread increase in cortical and subcortical NGF. Although a correlation with ChAT activity was not observed in cortex, the AD-related decline in NGF found in nbM is consistent with the possibility of impaired retrograde transport of NGF to this region.

The Macro Flow Planktometer: a new device for volume and fluorescence analysis of macro plankton including triggered video imaging in flow.

A newly developed macro flow planktometer is described for measuring plankton organisms with a size of 100-2,000 microns by the flow principle in time-saving and noncontact fashion. Based on the method of changes in electric resistance (Coulter principle), the device allows determination of the body volume of living organisms in their natural medium (fresh or seawater) at a measuring rate of up to 50 organisms per second. Simultaneous, laser-excited fluorescence measurement permits quantitative detection of fluorescent substances within the organisms. Controlled by the multiparametric measurement, video images of organisms of particular interest can be taken in the flow chamber using a stroboscopic imaging system. Valuable morphological information on the material under test is thus available in addition to the analytical measurement. Data acquisition and imaging, the total system control, and the fast data evaluation are performed with an IBM-AT compatible computer using an extensive software package. The easy-to-handle desktop unit can be used both in land laboratories and on ships. The modular structure of the system permits any desired combination of individual components to adapt it to various requirements. The operability of this new measuring system is demonstrated by several applications.

Increased NGF-like activity in young but not aged rat hippocampus after septal lesions.

Sympathetic sprouting in the hippocampus following septal denervation is thought to involve nerve growth factor (NGF). This sprouting response is dramatically reduced in aged rats, but immunological assays reveal no age-related decline in hippocampal NGF levels. In the present study, both a bioassay and an immunoassay were used to examine the effect of a medial septal lesion on hippocampal NGF levels in young adult (2-5 months) and aged (24 months) Fischer 344 rats. No significant differences were detected between normal young and aged rats, in agreement with earlier results. Following medial septal lesions, however, only young rats demonstrated significant increases in hippocampal NGF-like activity. These results support the hypothesis that the age-related deficit in sympathetic sprouting results from an attenuated neurotrophic response to hippocampal denervation.

Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease.

A two-site ELISA and a bioassay were used to detect NGF-like activity in human brain tissue. Both assays detected mouse NGF and recombinant human NGF with approximately equal sensitivity, whereas the antibodies showed little cross-reactivity with the recombinant human proteins NT-3 and brain-derived neurotrophic factor. NGF-like activity was detected in fresh human cortical samples obtained from epileptic patients, with the highest activity observed in the right hemisphere of men. NGF-like activity was subsequently measured in autopsy samples of frontal and occipital cortex from patients with Alzheimer's disease (AD) and from individuals with no history or pathological evidence of AD. Based on both the ELISA and the bioassay measurements, NGF-like activity was significantly elevated in both brain regions in AD. These results demonstrate the feasibility of detecting NGF-like activity in both fresh and postmortem human brain tissue and further suggest that AD is characterized by increased, rather than decreased, levels of cortical beta-NGF. The AD-related increase in NGF may be a consequence of degenerative changes in the basal forebrain cholinergic system.

Neurite outgrowth on postmortem human brain cryostat sections: studies of non-Alzheimer's and Alzheimer's tissue.

An in vitro assay to test for regional differences in neurite growth-promoting and growth-inhibiting factors in tissue sections of CNS tissue has been adapted to the use of postmortem human brain tissue. Frozen sections of the temporal lobe from victims of Alzheimer's disease were used as substrates for sympathetic neurite outgrowth in tissue culture. Tissue sections from a non-Alzheimer's brain were used as a control. Both explanted chick sympathetic ganglia and dissociated chick sympathetic neurons were cultured for 3 to 5 days on tissue sections in the presence of exogenous nerve growth factor. The dichotomy between gray and white matter portions of the tissue sections in supporting neurite outgrowth that was previously reported for fresh frozen human brain tissue was also found to persist in postmortem tissue. In addition, the total neurite outgrowth from explanted sympathetic ganglia was found to be significantly less on postmortem sections when compared with previous results obtained from fresh frozen tissue samples of epileptic tissue. Dissociated neurons exhibited neurite outgrowth on Alzheimer's sections that showed preferential growth on blood vessel segments but no affinity for senile plaques. The results suggest that there is some decline in the neurite growth-promoting ability of cortical gray matter obtained from postmortem-derived brains when compared with fresh tissue and that senile plaques do not represent sites of neurite stimulation in this in vitro system.

Hippocampal NGF levels are not reduced in the aged Fischer 344 rat.

The sympathetic sprouting response that occurs in the rat hippocampal formation following septal denervation is reduced in aged rats. Since considerable evidence implicates NGF-like activity in eliciting the sprouting, the simplest explanation for the age-related decline in sympathetic sprouting is a reduction in hippocampal NGF levels. In the present study, hippocampal NGF levels were measured using a 2-site ELISA in four different age groups of Fischer 344 rats. There was no decline in NGF levels with age, nor did we find any differences between male and female rats. This contradicts an earlier report in which a 40% reduction in hippocampal NGF protein levels was found in aged rats. Possible reasons for this discrepancy are discussed. The present results do not support the hypothesis that the age-related decline in sympathetic sprouting is due to a reduction in total hippocampal NGF levels.