Lack of association between polymorphisms of the toll-like receptor 4 gene and cerebral ischemia

Abstract. Toll-like receptor-4 (TLR4), an important mediator of the innate immune response, is expressed in atherosclerotic lesions. The common single nucleotide exchange (Asp299Gly) of the TLR4 gene has been previously reported to impair TLR4 function and to be associated with a decreased risk of carotid atherosclerosis. Therefore, we aimed to detect the potential impact of TLR4 genotypes on the risk of cerebral ischemia.We studied the prevalence of two common polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) in 3 independent study populations: (1.) in a cross-sectional study including 769 patients either with type 1 or type 2 diabetes mellitus, of whom 56 (7.2%) had a history of cerebral ischemia (study 1), (2.) a case-control study (study 2) including 128 consecutive patients with cerebral ischemia, mean age 60 ± 10.9 years and 139 control subjects, and (3.) a case-control study (study 3) including 171 young adults aged < 50 years with cerebral ischemia and 204 control individuals. In all subjects, Asp299Gly and Thr399Ile were detected by restriction length analysis.The prevalence of the TLR4 genotypes was essentially the same between patients with cerebral ischemia and control subjects in all 3 study populations. Furthermore, there was also no association with the subgroup of atherosclerotic stroke in both case-control studies populations.Although TLR4 polymorphisms are associated with a decreased risk of carotid atherosclerotic lesions, our findings indicate that they do not influence the prevalence of cerebral ischemia. This implies that the Asp299Gly TLR4-allele might have a protective role in carotid atherosclerosis, but not in cerebral ischemia.* both authors contributed equally to this work     

Safety of latest-generation self-expanding stents in patients with NASCET-ineligible severe symptomatic extracranial internal carotid artery stenosis

BACKGROUND: Patients with symptomatic extracranial internal carotid artery stenosis (> or =70%) benefit from carotid endarterectomy when compared with medical management. However, independent risk factors can significantly increase the combined stroke and death risk after carotid endarterectomy. Carotid angioplasty and stenting (CAS) is a therapeutic option in patients who are otherwise at high risk or ineligible for carotid endarterectomy. Previous-generation self-expanding stents were hampered by length foreshortening, which limited their application in multifactorial occlusive extracranial internal carotid artery stenosis. METHODS: This is a single-center, prospective, open-label, safety study of CAS with the latest-generation self-expanding stents in patients with extracranial internal carotid artery symptomatic stenosis (> or =70%). All patients included were adjudicated to be ineligible for carotid endarterectomy by a vascular surgeon and/or a neurologist according to the exclusion criteria. Primary adverse events included death and all strokes (ipsilateral and contralateral). Secondary adverse events included transient ischemic attack, myocardial infarction, stent thrombosis, need for reintervention, and presence of hematomas. All adverse events were recorded at 24 hours, 30 days, and 6 months after CAS. RESULTS: Between June 1, 2001, and January 30, 2003, 23 consecutive patients (14 women and 9 men; mean age, 65 years; age range, 48-85 years) underwent 24 extracranial CAS procedures with the latest-generation self-expanding stents. All patients had one or multiple criteria for ineligibility according to the North American Symptomatic Carotid Endarterectomy Trial. Extracranial CAS was successful in all patients, with average residual stenosis of less than 20%. One patient (4%) experienced a stroke by the 30-day periprocedure examination. The total number of primary adverse events at 6 months after CAS was 2 strokes (9%), 1 of which was contralateral to the stent placement; there were no deaths. Twenty-two patients were asymptomatic at 6 months, with a modified Rankin scale score of 1 or less. Of the 2 patients who had a stroke, 1 had a follow-up modified Rankin scale score of 3. CONCLUSION: Extracranial CAS with the latest-generation self-expanding stents is a valid alternative treatment in high-risk or North American Symptomatic Carotid Endarterectomy Trial-ineligible patients.     

Right ventricular myocardial responses to chronic pulmonary regurgitation in lambs: disturbances of activation and conduction

Patients after repair of tetralogy of Fallot are at increased risk of arrhythmic death. Clinical data suggest that pulmonary regurgitation predisposes to these arrhythmias, although the cellular electrophysiologic effects of pulmonary regurgitation are unknown. We induced pulmonary regurgitation in lambs, and 3 mo later, having quantified the pulmonary regurgitant (PR) fraction, studied right ventricular mechanical and electrophysiologic properties in vivo and in vitro. The PR fraction was greater in PR (75 +/- 10%) than in sham-operated animals (8 +/- 4%; p < 0.01). In vivo, monophasic action potential duration and activation time, at rest and during acute right ventricular stretch, were similar in both groups. However, the dispersion of activation time was greater in PR animals at rest (13 +/- 1.1 versus 8 +/- 1.1 ms; p < 0.05). Furthermore, the dispersion of activation increased during right ventricular stretch in PR, but not in sham-operated animals. In vitro, myocardial force-frequency responses were similar in both groups, indicating preserved systolic performance, but mechanical restitution studies showed a prolonged refractory period (447 +/- 22 versus 370 +/- 26 ms; p < 0.05) and a decreased recovery time constant (184 +/- 19 versus 265 +/- 20 ms; p < 0.001) in PR animals, indicating altered calcium cycling. Furthermore, the myocardial conduction velocity was reduced in PR animals (31 +/- 3.58 versus 47.9 +/- 5.1 cm/s; p < 0.01), resulting from a 2-fold increase in intracellular resistance (437.25 +/- 125.93 versus 194 +/- 43.27 Omega. cm; p = 0.025). Chronic PR leads to inhomogeneity of right ventricular activation, alters myocardial calcium cycling, reduces conduction velocity, and increases intracellular resistivity. These may contribute to the development of arrhythmias associated with PR, including those in patients after tetralogy repair.     

Glutamate uptake in cultured astrocytes depends on age: a study about the effect of guanosine and the sensitivity to oxidative stress induced by H(2)O(2)

Relatively few studies have been conducted to investigate the relationship between glutamate and development and/or aging. Rat cortical astrocyte cultures were used as a model to investigate glutamate uptake during development. The immunocontent of the markers glial fibrillary acidic protein (GFAP) and S100B increased, while basal secretion of S100B decreased, in astrocytes from 10 to 40 days in vitro (DIV). Basal glutamate uptake increased with age. Exposure to hydrogen peroxide decreased glutamate uptake more potently at 40 than 10 DIV. Moreover, 40 DIV astrocytes showed earlier loss of integrity (at 6 h) than 10 DIV astrocytes (at 24 h) after H(2)O(2) exposure. Addition of guanosine stimulated glutamate uptake only in 10 DIV astrocytes. The present work shows that mature astrocytes in culture present some neurochemical alterations also observed in astrocytes of aged animals. These results can contribute to the understanding of some consequences of the excitotoxicity and oxidative stress during brain aging.     

Sperm retrieval procedures and intracytoplasmatic spermatozoa injection with epididymal and testicular sperms

INTRODUCTION: Male infertility caused by azoospermia due to non-reconstructable obstruction or non-obstructive azoospermia can be treated by microsurgical epididymal aspiration (MESA) or testicular sperm extraction (TESE) followed by an intracytoplasmatic spermatozoa injection (ICSI). MATERIAL AND METHODS: From 9/93 to 6/01, we carried out 1,025 ICSI procedures with aspirated epididymal or testicular sperms in 684 cases. 163 ICSI cycles were performed with epididymal sperms and 862 ICSI cycles with testicular sperms or spermatids. The TESE was carried out by open biopsy, frequently in a multilocular technique. The aspirated spermatozoas were used after cryopreservation (frozen) or immediately after aspiration (fresh). RESULTS: 538 patients had obstructive azoospermia or ejaculation failure. In 487 cases the underlying cause of azoospermia was an impaired spermatogenesis, following maldescensus testis, chemotherapy, radiotherapy, or caused by Sertoli-cell-only syndrome, a genetic disorder or an unknown etiology. The transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal sperms in the cases of seminal obstruction (28% average birth rates in both cases). However, highly significant was the difference in birth rates with regard to the underlying cause of infertility. In contrast, in treating non-obstructive azoospermia we observed a birth rate of 19% per cycle. In all patient groups the birth rate with fresh spermatozoas did not differ from those with cryopreserved spermatozoa. 40% of patients after multilocular TESE showed clinical signs of testicular lesion. CONCLUSION: The underlying cause of azoospermia is the most important factor for the outcome of ICSI using epididymal and testicular sperms. In cases of non-obstructive azoospermia, the pregnancy rate is low compared with the results in cases of obstructive azoospermia. There is no difference between fresh and cryopreserved sperms. TESE with ICSI is the most efficient treatment of azoospermia caused by hypergonadotropic hypogonadism. The morbidity of the TESE procedure is highly relevant and must be considered if this technique is indicated.     

Spontaneous hemorrhage associated with a pilomyxoid astrocytoma. Case report

Pilomyxoid astrocytomas have been identified as a more aggressive variant of pilocytic astrocytomas that occur in infants and in young children. These tumors are characterized by a perivascular arrangement of pilocytic cells that has a monomorphous architecture with uniform, elongated bipolar cells loosely ranged within a prominent myxoid background. The authors present the case of a 24-year-old man with a pilomyxoid astrocytoma of the temporal lobe, who presented with a hemorrhage. The patient underwent gross-total tumor resection, and no evidence of residual or recurrent tumor was found on magnetic resonance images at the 6-month follow-up examination. The occurrence of a pilomyxoid astrocytoma in an adult suggests that this tumor is not limited to children. The tumor described in this report is unique because of its presentation with a hemorrhage, which has not been previously described in cases of pilomyxoid astrocytomas and is rarely found in those of pilocytic astrocytomas. Although this tumor predominantly exhibited the pattern of a pilomyxoid astrocytoma, there was a small focus of pilocytic astrocytoma, indicating that there is a spectrum of histological components found in these tumors and that certain elements may be associated with a more aggressive phenotype. In this paper the authors review the literature on pilomyxoid astrocytomas and discuss the unique aspects of this particular tumor presentation.     

Komplikationen der transrektalen Prostatabiopsie

Zusammenfassung Die Prostatabiopsie hat in den letzten 2 Dekaden einen dramatischen Wandel erfahren. Durch die Einführung des prostataspezifischen Antigens (PSA) in die Diagnostik des Prostatakarzinoms und die zeitgleiche Entwicklung moderner Biopsietechniken hat die Anzahl von transrektalen Prostatabiopsien deutlich zugenommen. Gleichzeitig sind die schwerwiegenden Komplikationen seltener geworden.Zu den schwerwiegenden Komplikationen nach Biopsie gehören septische Komplikationen (ca. 1%), rektale Blutungen (ca. 0,1%) und Harnverhaltungen (0,5%). Weniger schwerwiegende Komplikationen, wie das Auftreten von Fieber ohne septische Zeichen, findet sich in einer Häufigkeit von ca. 3,5%.Zu den häufigen, jedoch im Regelfall nicht behandlungsbedürftigen Komplikationen zählt die Makrohämaturie die bei nahezu 50% aller Patienten beobachtet wird. Das Gleiche gilt für die Hämatospermie in ähnlicher Größenordnung.Bei den insgesamt selten schwerwiegenden Komplikationen nach Prostatabiopsie ist ein rasches, zielgerichtetes Handeln erforderlich. Damit ist heute die Prostatabiopsie ein insgesamt komplikationsarmes, sicheres diagnostisches Verfahren mit einem außerordentlich hohen Stellenwert in der täglichen urologischen Praxis.

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Effect of carotid artery stenting on the external carotid artery

OBJECTIVE: We studied the fate of the ipsilateral external carotid artery (ECA) after stenting of the internal carotid artery (ICA) compared with the contralateral ECA. SUBJECTS AND METHODS: One hundred twenty-one ipsilateral ECAs in 112 consecutive patients who underwent carotid artery Wallstent placement were prospectively studied with color-coded duplex sonographic scanning (CCDS) and compared with 83 contralateral ECAs over 2 years. CCDS was scheduled for the day before (day 0), the day after (day 1) and 3, 6, 12, and 24 months after stenting. Development of ECA occlusive disease was evaluated with ECA-common carotid artery flow ratio (peak systolic velocity). For estimation of ECA stenosis 70% or greater, flow ratio 4.1 was used as the cutoff point. RESULTS: Before and after stenting, two and three (one additional) ECA occlusions were seen. Median grade of ECA stenosis on day 1 did not significantly change at angiography (P = 1.0; tendency of increase) or CCDS (P =.27; tendency of decrease).At follow-up (day 1-24 months, CCDS only), frequency of stenosis 70% or greater in the ipsilateral ECA was 21 of 120 (17.5%) on day 1 and 41 of 107 (38.32%) at 24 months, and 3 of 107 (2.5%) and 5 of 107 (4.67%) ECA occlusions were registered at the two time points. Progression of disease, as demonstrated by increase in flow ratio over time, was much more pronounced in the ipsilateral ECAs compared with the contralateral ECAs (P =.0002).In stented ICA, 2 (1.85%) asymptomatic recurrent stenoses 70% or greater were found at CCDS.One of three patients with new ECA occlusions reported jaw claudication for 10 days. Perioperative stroke (one major, four minor) occurred in 5 of 121 patients (4.46%). Two minor strokes caused by embolization occurred during the first year. CONCLUSION: The more pronounced progression of arteriosclerotic disease at the orifice of the ipsilateral ECAs during the first year after carotid stenting might be due to local factors of the ICA stent. Its clinical significance in respect to the effect of the ECA as collateral supply to the brain might depend on the incidence of carotid stent rerecurrent stenosis, which was low in the present study.