Dynamic behaviour of selected PET tracers in embryonated chicken eggs

La tomografía por emisión de positrones/tomografía computarizada (PET/TC) es una técnica establecida en la investigación preclínica de enfermedades en modelos de animales peque˜nos y en el diagnóstico clínico de cáncer. Esta técnica combina la información funcional del biomarcador emisor de positrones con los datos anatómicos de la imagen TC, permitiendo de este modo la investigación in vivo de los procesos biológicos en 4 dimensiones. Recientemente, el crecimiento de los huesos de los embriones de pollo se ha podido monitorizar usando PET/TC con 18F fluoruro como trazador óseo. Estamos interesados en la investigación de otros trazadores PET/TC en embriones de pollo como sistema de modelo in vivo. Para ello, evaluamos varios radiotrazadores usados habitualmente en pruebas clínicas o sintetizamos aquellos que no estaban disponibles comercialmente. Utilizando un microPET/TC de animales peque˜nos, evaluamos las características de 18F, 68Ga y 64Cu cloruro en huevos con sondaje. La 2-Deoxy-2[18F]fluorodeoxiglucosa (18F FDG) estaba absorbida en los sitios de crecimiento de los huesos. El 64Cu cloruro y un anticuerpo de unión a fibrillas de amiloide marcado con 68Ga se acumularon en el hígado, mientras que el 68Ga ligado a un conjugado de desferroxamina disminuyó con el tiempo en ese mismo órgano. Los resultados indican que estos biomarcadores pueden ser utilizados para la monitorización de procesos biológicos en huevos de pollo como modelo animal (AU)

Positron emission tomography/computer tomography (PET/CT) is an established method in preclinical research in small animal disease models and the clinical diagnosis of cancer. It combines functional information of the positron-emitting biomarker with the anatomical data obtained from the CT image. Thus, it allows for 4D in vivo investigation of biological processes. Recently, PET/CT was used to monitor bone growth of chicken embryos using 18F-fluoride as a bone-seeking tracer. We are interested in investigating the adequacy of additional PET/CT tracers in chicken embryos as an in vivo model system. For this reason, we evaluated several positron emitting compounds typically used in clinical tests or if these were not commercially available, we synthesised them. We studied the properties of these 18F- and 68Ga-labelled tracers and of 64Cu-chloride in catheterised eggs via small animal microPET/CT. 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG) was primarily absorbed at the sites of bone growth. 64Cu chloride and a 68Ga-labelled amyloid-fibril-binding antibody accumulated in the liver, while the 68Ga-albumin desferrioxamine conjugate signal in liver decreased over time. These results indicate that these biomarkers can potentially be used for the monitoring of biological processes in chicken eggs as an animal model (AU)

Dynamic behaviour of selected PET tracers in embryonated chicken eggs.

Positron emission tomography/computer tomography (PET/CT) is an established method in preclinical research in small animal disease models and the clinical diagnosis of cancer. It combines functional information of the positron-emitting biomarker with the anatomical data obtained from the CT image. Thus, it allows for 4D in vivo investigation of biological processes. Recently, PET/CT was used to monitor bone growth of chicken embryos using (18)F-fluoride as a bone-seeking tracer. We are interested in investigating the adequacy of additional PET/CT tracers in chicken embryos as an in vivo model system. For this reason, we evaluated several positron emitting compounds typically used in clinical tests or if these were not commercially available, we synthesised them. We studied the properties of these (18)F- and (68)Ga-labelled tracers and of (64)Cu-chloride in catheterised eggs via small animal microPET/CT. 2-Deoxy-2-[(18)F]fluoroglucose ([(18)F]FDG) was primarily absorbed at the sites of bone growth. (64)Cu chloride and a (68)Ga-labelled amyloid-fibril-binding antibody accumulated in the liver, while the (68)Ga-albumin desferrioxamine conjugate signal in liver decreased over time. These results indicate that these biomarkers can potentially be used for the monitoring of biological processes in chicken eggs as an animal model.

[Clinical aspects of puerperal psychoses. Review with 3 case examples]. / Klinische Aspekte der Wochenbettpsychosen. Ubersicht mit drei Fallbeispielen.

Psychic disturbances in the post-partum period are divided into the postpartum blues, postpartum depression, and postpartum psychoses. The latter are severe endogenous psychoses which mostly fulfill the diagnostic criteria for cycloid psychoses according to Leonhard. Based on three case reports, characteristic symptoms, the phasic clinical course with remissions, and distinct etiological, therapeutic, and forensic aspects of cycloid psychoses in the post-partum period are discussed. The high relapse rate of approximately 50% in patients at risk requires intensive psychiatric care in the peripartal period. In particular, the possibility of a prophylactic treatment of patients at risk with lithium immediately after delivery is emphasized. However, this sophisticated therapeutic strategy requires close cooperation between gynecologists and psychiatrists.

Vardenafil increases penile rigidity and tumescence in erectile dysfunction patients: a RigiScan and pharmacokinetic study.

The pharmacodynamic effect on penile rigidity and tumescence and the pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil, a new PDE5-inhibitor, were investigated in 21 erectile dysfunction patients. Patients were evaluated with RigiScan on three occasions in a randomized, placebo-controlled, double-blind crossover fashion, while receiving visual sexual stimulation. Relative to placebo, a single dose of 10 mg vardenafil led to a mean increase in the duration of >60% penile rigidity of 24.4 min (95% CI: 7.4 to 41.3) at the base and of 24.8 min (8.5 to 41.1) at the tip. For the 20-mg dose, the increase in duration of > 60% penile rigidity relative to placebo was 37.2 min (20.2 to 54.1) at the base and 28.7 min (12.7 to 44.7) at the tip. Single doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations of vardenafil, with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of 9.1 microg/l (geometric SD = 1.63) and 20.9 microg/l (geometric SD = 1.83), respectively. In the post-absorptive phase, the concentrations declined with an average terminal t 1/2 of 4.2 h (geometric SD = 1.27) and 3.9 h (geometric SD = 1.31). The systemic exposure of vardenafil expressed as AUC normalized for dose and body weight was dose-proportional (associated 90% CI: -4 to 30%) as well as Cmax (associated 90% CI: -12 to 33%). The treatments were well tolerated. There was a small, clinically irrelevant reduction in blood pressure with a small compensatory rise in heart rate. There were no electrocardiographic effects or relevant changes of the safety laboratory screens. The observed pro-erectile properties, pharmacokinetic characteristics and safety profile make vardenafil a suitable candidate for further evaluation in the treatment of erectile dysfunction.

Evaluation of attention process training and brain injury education in persons with acquired brain injury.

Fourteen patients with stable acquired brain injuries exhibiting attention and working memory deficits were given 10 weeks of attention process training (APT) and 10 weeks of brain injury education in a cross-over design. Structured interviews and neuropsychological tests were used prior to rehabilitation and after both treatments to determine the influence of the interventions on tasks of daily life and performance on attentional networks involving vigilance, orienting, and executive function. The overall results showed that most patients made improvements. Some of these gains were due to practice from repetitive administration of the tests. In addition, the type of intervention also influenced the results. The brain injury education seemed to be most effective in improving self-reports of psychosocial function. APT influenced self-reports of cognitive function and had a stronger influence on performance of executive attention tasks than was found with the brain injury education therapy. Vigilance and orienting networks showed little specific improvement due to therapy. However, vigilance level influenced the improvement with therapy on some tests of executive attention. We consider the implications of these results for future studies of the locus of attentional improvement and for the design of improved interventions.

[Testicular metastasis of prostatic carcinoma 3 years after subcapsular orchiectomy. A case report]. / Hodenmetastase eines Prostatakarzinoms drei Jahre nach subkapsulärer Orchiektomie. Ein Fallbericht.

Metastatic cancer to the testis is a rare phenomenon of prostate carcinoma with only 80 cases reported in the literature. Most of these secondary testicular tumors were diagnosed on routine pathohistological examination of testicular tissue after plastic orchiectomy. In none of these cases metachronous development of these metastases has been described. For the first time we report on a 75-year old patient who developed a prostate carcinoma metastatis to the right testicle three years after undergoing subcapsular orchiectomy. This case shows that the urologist has to think about a metastatic cancer when he sees a testicular tumor also after plastic orchiectomy.

Loss of functional hemispheric asymmetry in Alzheimer's dementia assessed with near-infrared spectroscopy.

In a total of 10 patients with dementia of the Alzheimer-type (DAT) and in 10 healthy controls near-infrared spectroscopy (NIRS), a new non-invasive optical method, was used to measure the changes of concentrations of oxy- (O2HB) and deoxyhemoglobin (HHB) in left and right hemispheric prefrontal brain tissue areas during performance of the Verbal Fluency Test (VFT). On a neuropsychological level, the healthy subjects performed better in the VFT than patients with DAT. Statistical analysis of the relative concentrations of O2HB and HHB measured with NIRS during performance of the VFT revealed a significant interaction of the hemispheric effects with the diagnosis. A possible interpretation of this finding is that a good performance in the VFT relies on a predominantly left hemispheric activation observed in controls, whereas a low number of correct responses is associated with a loss of this asymmetric activation in patients with DAT. Although both, patients and controls, performed better in the category version of the VFT, the metabolic effects of this task were significantly less pronounced than in the letter version. This indicates that different energy demands, according to the type of access to the memory stores, may be interpreted as the result of a less energy-demanding access to categorically stored information and adds further evidence to the view that memory departments in humans are organized according to categorical principles.

[Pharmacotherapy of Alzheimer dementia: therapy of cognitive symptoms--new results of clinical studies]. / Pharmakotherapie bei Alzheimer-Demenz: Therapie kognitiver Symptome--neue Studienresultate.

Recent investigations have given new insights into pathogenetical determinants of Alzheimer's disease. Amyloid deposition and neurofibrillary tangles are no longer considered to be primary pathological changes. Neurobiological research tries to work out the etiopathogenital cascade that finally causes Alzheimer's disease. So far, several relevant pathogenetical factors have been detected, e.g. pertubated control of glucose breakdown, impairment of oxidative metabolism, impaired neuroprotection due to increased oxidative stress and non-enzymatic protein glycation as well as immunological disturbances. Thus, new strategies for the development of cognition-enhancing drugs are emerging. The authors review reports on agents, that are under investigation for the treatment of cognitive symptomatology in Alzheimer's disease. Some of these agents have already been used for treatment of other medical conditions, e.g. nimodipine, memantine as well as selegiline. Many of them are still experimental. Promising strategies include antioxidative agents (e.g. vitamin E, vitamin C, beta-carotin), acetylcholinesterase-inhibitors with central selectivity (e.g. ENA 713), M1- and M4-muscarinic receptor agonists (milameline) as well as sabeluzole, a benzothazide derivative that shows neurotrophic activities and anti-inflammatory substances like indomethacin.

Auditory P300 topography and neuropsychological test performance: evidence for left hemispheric dysfunction in schizophrenia.

Asymmetrical topography of the auditory P300 with reduced left hemispheric amplitudes and, consequently, a right-lateralized peak of the P300 electrical field has been repeatedly reported in schizophrenia. This was interpreted as an indication of reduced left-hemispheric activity during the simple cognitive P300 task. Since generator locations calculated from the surface potentials are ambiguous, further evidence is required to support this conclusion. In the present study, 13 stabilized DSM-III-R schizophrenic patients were studied with an auditory P300 paradigm and neuropsychological methods sensitive to functional brain asymmetries. The tests included the verbal paired associates test (Goldstein et al 1988, Cortex 24:41-52) and the nonspatial conditional associative learning test (Petrides 1985, Neuropsychologia 23:601-614). A significant correlation was found between right-sided lateralization of the P300 maximal positivity and neuropsychological evidence for left hemispheric temporal- hippocampal dysfunction. Attentional performance was correlated with P300 amplitudes. The results of this study provide further evidence that right-sided lateralization of the P300 peaks results from dysfunction of left-hemispheric neuronal generators.

Cerebellar arachnoid cyst in a firesetter: the weight of organic lesions in arson.

A 52-year-old female patient was accused of arson; the patient had had an arachnoid cyst of the cerebellar vermis. Even after surgery, she showed marked instability of mood and pseudologia fantastica, but did not suffer from cognitive impairment. Possible associations of the presence of this cerebellar arachnoid cyst and behavioral disturbances are discussed.

Postpartum blues: relationship between not-protein bound steroid hormones in plasma and postpartum mood changes.

The relationship between non-bound steroid hormone levels in plasma and the occurrence of postpartum mood changes was investigated in 26 newly delivered mothers throughout the first 5 days postpartum. Studies with saliva samples had reported higher concentrations of 17 beta-estradiol and progesterone on the days of symptoms in women experiencing postpartum blues. As there had been a controversy as to how far saliva concentrations reflect free hormone levels in plasma, free hormone levels of 17 beta-estradiol and progesterone were determined in plasma using ultrafiltration. No significant difference concerning free hormone levels could be found between women with and without postpartum blues.

[Progressive paralysis: prognostic indications by modern imaging procedures. A case report]. / Progressive Paralyse: Prognosehinweise durch moderne bildgebende Verfahren. Ein Fallbeispiel.

The case of a patient with early diagnosed neurosyphilis (general paresis) is presented. Modern neuroimaging techniques such as single photon emission computed tomography (SPECT) may give clues to the treatment outcome as early as 1 month after antibiotic treatment. Improvement of cognitive functions was accompanied by normalization of the initially altered P300-topography.

Post partum blues: depressive disease or pseudoneurasthenic syndrome.

Depressive mood disorders following childbirth can be quantified with self-rating and observer-rating scales. During two months, in the period from November 1989 to March 1990, women admitted to the obstetric unit of the University of Würzburg were examined on days 3 and 5 post-partum with the Hamilton Psychiatric Rating Scale for Depression, the Montgomery-Asberg-Depression-Rating-Scale and the Befindlichkeits-Scale by von Zerssen. Results reveal that during the early puerperium, scores on these scales rarely reach the same severity as in major depressive disorder. The clinical picture is no different from emotional-hyperaesthetic hyposthenia following other kinds of physical illness such as endocrine disorders.

[Long-term coverage of defect-wounds using synthetic skin substitute]. / Langfristige Deckung von Defektwunden mit synthestischem Hautersatz.

According our experiences non-infected defect wounds can be covered with Epigard even for a long time without problems. Changing the skin substitute is not necessary. Thus the danger of bacterial contamination is reduced and a reliable prevention of infection results. Weeks or months later an ideal base for autodermic grafting is obtained. Our method is indicated particularly for treatment of open fractures with skin defects. Long-term cover of infected tissue cannot always be achieved; in this case another therapeutic way should be attempted.