Material-Specific Roadmap Modes Can Improve the Visibility of Liquid Embolic Agents for Endovascular Embolization: A Systematic In Vitro Study.

BACKGROUND AND PURPOSE: Endovascular embolization using liquid embolic agents is a safe and effective treatment option for AVMs and fistulas. Because reliable visibility of these liquid embolic agents is essential for intraprocedural visual control to prevent complications, novel angiographic systems are equipped with material-specific roadmap modes. The aim of this study was the systematic in vitro comparison of conventional and material-specific roadmap modes regarding the visibility of the most used liquid embolic agents. MATERIALS AND METHODS: A recently introduced in vitro model, resembling cerebral vessels, was embolized with Onyx 18, Squid 18, PHIL 25%, and n-BCA mixed with iodized oil (n = 4 for each liquid embolic agent), as well as with contrast medium and saline, both serving as a reference. Imaging was performed in conventional and material-specific roadmap modes. The visibility of the liquid embolic agents in both modes was compared quantitatively and qualitatively. RESULTS: Significant differences between conventional and material-specific roadmap modes regarding the visibility of the liquid embolic agents were observed for all study groups. All liquid embolic agents were better visible in the material-specific roadmap modes compared with the conventional mode in qualitative and quantitative analyses (eg, Onyx in conventional-versus-material-specific modes along the 1.0-mm sector: mean contrast-to-noise ratio, 5.69 [SD, 0.85] versus 47.18 [SD, 5.72]; P < .001, respectively). CONCLUSIONS: In this in vitro study, we demonstrated a better visibility of all investigated liquid embolic agents by using material-specific roadmap modes compared with the conventional roadmap technique. Especially in complex anatomic situations, these novel roadmap modes could improve the visual control and thus the safety and efficacy of embolization procedures in clinical practice.

[Cerebral MR imaging of malignant melanoma]. / Zerebrale MR-Bildgebung beim malignen Melanom.

CLINICAL/METHODICAL ISSUE: Melanoma is the third leading cancer entity to metastasize to the central nervous system (CNS) after lung and breast cancer. This is often an early event in the disease course and limits survival. Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases are commonly found in the subcortical white matter. The signal characteristics can vary substantially and may change over time due to hemorrhages or the accumulation of melanin and paramagnetic ions. It is not yet clear whether novel targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging characteristics. Also immune-related side effects, such as hypophysitis (in approximately 5 % of patients receiving ipilimumab therapy) or granulomatous disease (neurosarcoid) can occur. STANDARD RADIOLOGICAL METHODS: Melanoma metastases are usually hyperdense in computed tomography (CT). In magnetic resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained. Coronal and axial imaging planes should be scanned to cross-correlate findings. METHODICAL INNOVATIONS: Susceptibility-weighted imaging is a new sensitive method to detect melanoma metastases. Approximately 66 % of melanoma metastases show intratumoral susceptibility signals (ITSS). This sets them apart from other metastases (e.g. lung and breast cancer show less ITSSs, specificity approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain imaging. PERFORMANCE: Susceptibility-weighted imaging increases the sensitivity to detect metastases but lacks specificity. Differentiating metastases, microbleeding or calcification can be impossible. It is controversial how to interpret susceptibility signals without correlative signs on other sequences (differential diagnosis: metastasis, microbleeding and calcification). PRACTICAL RECOMMENDATIONS: CNS metastases are common in melanoma. MRI screening starting in stage IIc should be considered even in asymptomatic patients. Stage IV requires quarterly MRI examinations. Melanotic and amelanotic metastases show different MRI characteristics. The differentiation between metastasis and microbleeding can be impossible and might require a follow-up scan. Susceptibility-weighted imaging increases the sensitivity of metastases detection but lacks specificity. It can help to differentiate between different metastatic entities.

[Predictive factors for determination of menopausal age]. / Prädiktive Faktoren zur Bestimmung des Menopausealters.

In western Europe the average age at menopause is 52 years. This means that a woman spends approximately 30 years of her life in the postmenopausal status. The possibility to predict the actual age AT menopause would have major implications for family planning, sterility treatment and for the decision to apply HRT. There are numerous associations between socio-economic factors and the age at menopause. A positive correlation has been shown between cigarette smoking and menopausal age. Furthermore several lifestyle factors have an influence on the onset of menopause. However it is not clear in how far generative and socio-economic factors such as marital status interfere with ovarian function.

[Premenstrual syndrome]. / Das Prämenstruelle Syndrom.

The Premenstrual Syndrome (PMS) is defined as the repeated occurrence of psychic disability accompanied by physical symptoms such as weight-gain, mastodynia and edema during the luteal phase. Irritability, depressive mood, lack of concentration and anxiety are the dominant psychiatric features. These symptoms culminate during the premenstrual period and disappear at the onset of menstrual bleeding. The symptomatology is of variable degree. About 2 to 3% of all women of reproductive age are severely impaired by these symptoms. The etiology of PMS is unknown. Disturbance of serotonin metabolism in the central nervous system is discussed. Furthermore abnormalities of the metabolism of sex-steroids in the brain could be involved, since these metabolites are able to modulate the GABA-ergic system. This applies in particular to progesterone-metabolites. Other etiologic concepts favour the ideas of elevated aldosterone activity, variations of endogenous opiod-levels or transient hyperprolactinemia. Thus the unknown etiology and the complex pathophysiology explain the polypragmatic therapeutic strategies including psychotherapy, treatment with psychopharmacologic agents, administration of aldosterone-antagonists, GnRH-analoga and finally prescription of oral contraceptives. The management of PMS requires individualized care by primarily treating the leading symptoms.

[Premature climacteric as a special form of secondary ovarian insufficiency]. / Das Klimakterium Präcox als Sonderform der sekundären Ovarialinsuffizienz.

In western countries menopause is expected to occur at 50-52 years of age. Cessation of ovarian function before the age of 40 is defined as premature ovarian failure (POF). POF can be associated with chromosomal aberrations as well as with autoimmune diseases or general endocrine or metabolic disorders. Prevalence of POF is significantly increased in patients undergoing chemotherapy or radiation for treatment of malignant diseases. In some patients however etiology of POF remains unknown. Therefore therapeutic options are limited. For counseling patients it cannot be over-emphasized that HRT is mandatory to prevent long term symptoms of estrogen deprivation.

[Low-dose oral contraception and bone density]. / Niedrig dosierte orale Kontrazeptiva und Knochendichte.

Oral contraceptives (OC) with 20 or 30 mcg Ethinyl-Estradiol (EE) inhibit bone remodeling in all age groups investigated until today as far as the biochemical parameters are considered. In perimenopausal women, OC with 20 or 30 mcg EE reduce the decrease in bone density and may, depending on the starting point, induce an increase in bone density. OC with 20 mcg EE might impede the formation of a physiological peak bone mass in very young women (probably women less than 20 years of age) by a reduction of bone metabolism. This possibility provoked a certain insecurity. However, it should not lead to the consequence that a safe contraceptive method is refused to young women. Unfortunately, there is still a lack of reliable studies allowing a final statement on the effect of low-dose OC on bone density in teenagers. Such studies are urgently needed so that we are able to guarantee in very young women that a reasonable contraception has not to be payed by a long-term risk for the skeletal health. The administration of a progestagen-only pill might be an alternative method for contraception in adolescence. A preparation containing 30 mcg of Levonorgestrel, nearly out of use today, could be of particular interest. A British study (20) has shown that during regular peroral administration of 30 mcg Leveonorgestrel per day, mean serum estradiol concentration decreased only slightly, from 653 to 500 pmol/l. This Estradiol concentration should still allow a normal bone metabolism and therefore a normal formation of the peak bone mass. However, the data actually available do not point convincingly to the conclusion that OC with 20 mcg EE or less might result in an insufficient estrogen concentration for normal bone metabolism. To reach peak bone mass, other factors than estrogens only are needed, such as Calcium, Vitamin D and physical activity.

Tamoxifen for breast cancer prevention.

Tamoxifen is of proven efficacy in the treatment of breast cancer. New data indicate that it might be able to reduce the occurrence of receptor positive breast cancer when taken as a preventative. However trade-offs for this reduction are an increased incidence of endometrial carcinomas and thromboembolic events. Therefore the use of tamoxifen as preventative ought to be restricted to clinical studies or a well defined high risk situation. Whether raloxifen is superior to tamoxifen remains to be shown.

Elevated serum progesterone concentrations during the early follicular phase of the menstrual cycle: clinical significance and therapeutic implications.

This study describes the incidence and clinical significance of hyperprogesteronemia in the early follicular phase of the menstrual cycle and the effects of prednisolone treatment in patients with this condition. Progesterone, testosterone and dehydroepiandrosterone sulfate (DHEAS) serum concentrations were determined in 316 consecutive patients admitted for infertility treatment. Elevated concentrations of progesterone in the early follicular phase could be detected in 36 cases (11.4%). In these patients, elevated testosterone and DHEAS concentrations could be detected in eight and ten cases, respectively. Serum concentrations of 17 alpha-hydroxyprogesterone and cortisol were normal in all patients. Treatment with 2.5-7.5 mg prednisolone/day normalized progesterone serum concentrations within 4-8 weeks. Twenty-four patients achieved a pregnancy either by timed intercourse or by intrauterine insemination (IUI) over the following 12 months.

Mechanisms of enhanced lung injury during sepsis.

A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility to injury after a direct pulmonary insult (deposition of IgG immune complexes or airway instillation of lipopolysaccharide). By itself, cecal ligation/puncture did not produce evidence of lung injury. However, after a direct pulmonary insult, lung injury in septic animals was significantly enhanced. Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-alpha) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion or treatment with anti-C5a abolished all evidence of enhanced lung injury in septic animals. When stimulated in vitro, bronchoalveolar lavage macrophages from septic animals had greatly enhanced CXC chemokine responses as compared with macrophages from sham-operated animals or from septic animals that had been complement depleted. These data indicate that the septic state causes priming of lung macrophages and suggest that enhanced lung injury in the septic state is complement dependent and related to increased production of CXC chemokines.

Expression of interleukin-6 and interleukin-6 receptors in human granulosa lutein cells.

Cytokines are important regulators of reproductive functions. Significant amounts of interleukin-6 (IL-6) have been detected in the serum and ascites of patients with ovarian hyperstimulation syndrome (OHSS). These findings suggest the involvement of IL-6 as a mediator in the pathogenesis of OHSS. This study was performed to analyse IL-6 and IL-6 receptor (IL-6-R) expression in human granulosa lutein cells (GC). GC were cultured after isolation from follicular fluid. IL-6 concentrations in follicular fluid and serum from individual patients and GC supernatants were measured by enzyme-linked immunosorbent assay. We found detectable concentrations of IL-6 in serum and follicular fluid of all patients. Expression of IL-6 in GC was shown immunocytochemically. IL-6 mRNA was detected in GC by in-situ hybridization. Gene expression for IL-6 and IL-6-R in GC was demonstrated using reverse transcription-polymerase chain reaction. IL-6 significantly inhibited human chorionic gonadotrophin (HCG)-induced progesterone secretion of GC. The results of our study suggest that IL-6 is expressed in HGC and that this cytokine is able to modulate GC function via its specific receptor. This is the first report that describes the precence of IL-6-R in human granulosa lutein cells.

Fetal cerebral AV-malformation and cardiomegaly, diagnostic and therapeutic problems.

Intracerebral aneurysms are rare. However they are potentially life-threatening. Today by means of ultrasound investigations these malformations can occasionally be identified prenatally. In these cases questions of intrauterine therapy, mode and time of delivery and postnatal treatment have to be discussed with the parents. We describe two cases with prenatal diagnosis of intracerebral arteriovenous malformations, diagnostic workup, therapeutic options and fetal outcome.